Regulatory Peptides[JOURNAL]
Sun
200 papers
Toll-like receptor levels and caffeine responsiveness in rat pups during perinatal period.
Tunc T, Aydemir G, Karaoglu A … +6 more , Cekmez F, Kul M, Aydinoz S, Babacan O, Yaman H, Sarici SU
Regul Pept · 2013 Mar · PMID 23313844 · Publisher ↗
Infants born prematurely are prone to bronchopulmonary dysplasia which is a devastating form of chronic lung disease that develops in very low birth weight infants. Toll-like receptors (TLRs) are pattern recognition rece...
Infants born prematurely are prone to bronchopulmonary dysplasia which is a devastating form of chronic lung disease that develops in very low birth weight infants. Toll-like receptors (TLRs) are pattern recognition receptors that initiate innate immune responses. We tested TLR2, 4, and 9 levels in the lungs of rat pups given caffeine at the first days of postnatal life. Twenty-four rat pups equally divided into three groups. The study group received caffeine immediately after birth for ten days. The levels of TLR9 were found significantly higher in study group than control groups. We conclude that the beneficial and anti-inflammatory effects of caffeine in the lungs of newborn rats may be due to increased TLR9 levels.
Nesfatin-1 in advanced lung cancer patients with weight loss.
Cetinkaya H, Karagöz B, Bilgi O … +5 more , Ozgün A, Tunçel T, Emirzeoğlu L, Top C, Kandemir EG
Regul Pept · 2013 Feb · PMID 23269222 · Publisher ↗
The cachexia occurs frequently in lung cancer patients. Among appetite regulatory peptides, alteration of expressions of leptin and ghrelin is demonstrated in cachectic cancer patients, but nesfatin-1 has not been yet st...
The cachexia occurs frequently in lung cancer patients. Among appetite regulatory peptides, alteration of expressions of leptin and ghrelin is demonstrated in cachectic cancer patients, but nesfatin-1 has not been yet studied in cancer. We investigated serum nesfatin-1 level in advanced lung cancer patients. Forty-one lung cancer patients and 24 healthy subjects were included to the study. Nesfatin-1 serum levels were analyzed by ELISA kit. Serum nesfatin-1 levels were lower in lung cancer patients than in healthy subjects (0.52±0.19ng/ml vs 0.75±0.23ng/ml; p<0.001). In lung cancer patients with weight loss, nesfatin-1 levels were decreased compared to the patients without weight loss (0.44±0.16ng/ml vs 0.63±0.18ng/ml; p<0.001). Whereas, there were no any difference between patients without weight loss and control subjects (0.63±0.18ng/ml vs 0.75±0.23ng/ml; p:0.129) or between SCLC and NSCLC patients (0.53±0.18ng/ml vs 0.52±0.20ng/ml; p:0.458). No significant correlation was found between serum nesfatin-1 values and BMI. In conclusion, loss of fat mass may decrease serum nesfatin-1 level in lung cancer patients with weight loss. The future studies which explore biological significance of low serum nesfatin-1 level in cancer are needed.
Effect of glucagon-like peptide-2 exposure on bone resorption: Effectiveness of high concentration versus prolonged exposure.
Askov-Hansen C, Jeppesen PB, Lund P … +3 more , Hartmann B, Holst JJ, Henriksen DB
Regul Pept · 2013 Feb · PMID 23261963 · Publisher ↗
OBJECTIVE: In healthy subjects, subcutaneous injections of GLP-2 have been shown to elicit dose-related decrease in the bone resorption marker, carboxy-terminal telopeptide of type I collagen (CTX), and have been propose...
OBJECTIVE: In healthy subjects, subcutaneous injections of GLP-2 have been shown to elicit dose-related decrease in the bone resorption marker, carboxy-terminal telopeptide of type I collagen (CTX), and have been proposed for the treatment of osteoporosis. This study investigated the relation between GLP-2 exposure and decreases in CTX in order to determine whether high concentrations or prolonged exposure was the most effective mode of administration. High GLP-2 concentrations resulted from iv bolus injections, whereas a more protracted stimulation was obtained by subcutaneous injections and the addition of an inhibitor of GLP-2 degradation, a DPP-4 inhibitor, sitagliptin. MATERIALS AND METHODS: Eight healthy subjects were given: a) three intravenous injections of GLP-2 of 0.1, 0.4 and 0.8nmol/kg, b) one subcutaneous injection of 1.6mg GLP-2 and c) one subcutaneous injection of 1.6mg GLP-2 preceded by an intake of sitagliptin. Blood was sampled for measurements of GLP-2 and p-CTX after each intervention. RESULTS: The 0.1, 0.4 and 0.8nmol/kg GLP-2 injections dose-dependently elevated plasma GLP-2 concentrations and decreased CTX, but the decrease was similar regardless of dose. Subcutaneous GLP-2 caused a much more prolonged exposure (with a peak concentration corresponding to 0.4nmol/kg IV) and was associated with a stronger and a more prolonged suppression of CTX, but in spite of significantly increasing exposure, the administration of sitagliptin, had no additional effect. CONCLUSION: The high concentrations obtained by iv administration were less effective with respect to CTX suppression than the prolonged exposure (with much lower peak concentrations). GLP-2 agonists for osteoporosis treatment should therefore be long-acting for best efficacy.
Erythrocyte-based analgesic peptides.
Song CZ, Wang QW, Song CC
Regul Pept · 2013 Jan · PMID 23220007 · Publisher ↗
Human erythrocyte discards the major organelles in a bid to maximize cellular hemoglobin. Hemoglobin, approximately 98% of the intraerythrocytic protein, serves as the principle transport medium of gaseous conveyance. Th...
Human erythrocyte discards the major organelles in a bid to maximize cellular hemoglobin. Hemoglobin, approximately 98% of the intraerythrocytic protein, serves as the principle transport medium of gaseous conveyance. The accumulated data speaks in favor of erythrocyte not merely engaging in gas exchange, but building molecular signaling as a side job during its 4-month sojourn in blood circulation. The production mechanism of erythrocyte-based bioactive peptides is not clear. Recent studies indicate that proteasome and its subunits persist in mature erythrocyte. The intraerythrocytic proteasome is involved in the formation of hemoglobin-derived analgesic peptides and enables erythrocyte to exert the erythrocrine function. Erythrocrine describes erythrocyte for generation and excretion of signaling molecules and has the potential of shedding light on our understanding of novel actions of erythrocyte. Different types of erythrocrine analgesic peptides are originated from the intraerythrocytic degradation of hemoglobin and manifest the systemic influence in physiology and pathophysiology along its travel through the body via the bloodstream. Translational research from bench to bedside will expand our knowledge of erythrocrine concept and facilitate the development of therapeutic strategies for clinical pain.
Thymohexin exhibits cytoprotective effect in experimental gastric lesions in rats both through the inhibition of inducible nitric oxide synthase and reduction of oxidative mucosal damage.
Nasadyuk C, Sklyarov A
Regul Pept · 2013 Jan · PMID 23201077 · Publisher ↗
BACKGROUND AND OBJECTIVE: Some short peptides have recently been reported to exhibit gastroprotective properties but the role of NO-synthase system in these mechanisms still leaves much to be elucidated. That is why the...
BACKGROUND AND OBJECTIVE: Some short peptides have recently been reported to exhibit gastroprotective properties but the role of NO-synthase system in these mechanisms still leaves much to be elucidated. That is why the purpose of our study was to explore the gastroprotective effect of the hexapeptide Arg-α-Asp-Lys-Val-Tyr-Arg (thymohexin) under conditions of the modeling of iNOS activity. MATERIALS AND METHODS: The studies were performed on 80 outbred male rats. Gastric lesions were induced with epinephrine (2 mg/kg) or indomethacin (30 mg/kg). Fifteen minutes before the exposure to ulcerogens rats were pretreated with thymohexin alone and combined with l-arginine or aminoguanidine. Twenty-four hours later gastric mucosa damage, L-arginine/NOS/NO system, processes of lipoperoxidation, superoxide dismutase and catalase activity were assessed. RESULTS: Thymohexin markedly attenuated both epinephrine- and indomethacin-induced gastric ulceration in rats, decreasing the area and score of mucosal lesions (p<0.05), iNOS activity (p<0.05) and malonic dialdehyde content (p<0.05) in gastric mucosa. The cytoprotective effect of thymohexin was significantly enhanced by L-arginine and aminoguanidine. The combination of thymohexin and l-arginine was superior to that with aminoguanidine. CONCLUSIONS: Thymohexin protects gastric mucosa against epinephrine- and indomethacin-induced gastric lesions in rats. Thymohexin-induced gastroprotection is probably mediated by inhibition of iNOS and decrease of the oxidative damage in gastric mucosa.
cGMP-PDE3-cAMP signal pathway involved in the inhibitory effect of CNP on gastric motility in rat.
Cai YL, Sun Q, Huang X … +5 more , Jiang JZ, Zhang MH, Piao LH, Jin Z, Xu WX
Regul Pept · 2013 Jan · PMID 23186653 · Publisher ↗
In the present study, we investigated the mechanism of C-type natriuretic peptide (CNP)-induced inhibitory effect on spontaneous contraction of gastric antral smooth muscle to clarify CNP-NPR-B/pGC-cGMP downstream signal...
In the present study, we investigated the mechanism of C-type natriuretic peptide (CNP)-induced inhibitory effect on spontaneous contraction of gastric antral smooth muscle to clarify CNP-NPR-B/pGC-cGMP downstream signal transduction pathway using organ bath and ELISA methods in rat. CNP significantly reduced the amplitude of the spontaneous contraction and increased the contents of cGMP and cAMP in the gastric antral smooth muscle tissue. In the presence of IBMX, a non-selective phosphodiesterase (PDE) inhibitor, the inhibitory effect of CNP on spontaneous contraction was significantly suppressed; however, the production of cGMP but not cAMP was still increased by CNP. EHNA, a PDE2 inhibitor, did not affect both CNP-induced inhibition of the contraction and CNP-induced increase of cGMP and cAMP generations in gastric smooth muscle tissue, while milrinone, a PDE3 inhibitor, similar to IBMX, attenuated the CNP-induced inhibitory effect on spontaneous contraction and increased the content of cGMP but not cAMP. The results suggest that cGMP-PDE3-cAMP signal pathway is also involved in the CNP-induced inhibition of gastric motility in rat.
Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser Doppler flowmetry in end-jejunostomy short bowel syndrome patients.
Høyerup P, Hellström PM, Schmidt PT … +4 more , Brandt CF, Askov-Hansen C, Mortensen PB, Jeppesen PB
Regul Pept · 2013 Jan · PMID 23159451 · Publisher ↗
BACKGROUND: In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured direc...
BACKGROUND: In animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunostomy short bowel syndrome (SBS) patients. METHODS: In five SBS patients with end-jejunostomy a specially designed laser Doppler probe was inserted into the stoma nipple, and blood flow measured directly on the jejunal mucosa for 105 min in relation to no treatment, systemic saline infusion, topical adrenaline application and a subcutaneous injection of 800 μg native GLP-2. RESULTS: The GLP-2 injection increased jejunal mucosal blood flow by 79±37% compared to conditions, where no treatment was given (p<0.001). The significant effect was present at least 105 min. Systemic saline infusion and topical, mucosal adrenaline application did not affect mucosal microcirculation. CONCLUSIONS: GLP-2 raises jejunal microcirculation in SBS patients with end-jejunostomy. This may explain the redness and increase in the end-jejunostomy nipple size imminently after commencing GLP-2 injections. The potential beneficial effects of this GLP-2-mediated increase of blood flow in the mesenteric bed should be investigated in clinical conditions other than the short bowel syndrome.
Neuregulin-1β regulates tyrosine kinase receptor expression in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate.
Yue W, Song L, Fu G … +2 more , Li Y, Liu H
Regul Pept · 2013 Jan · PMID 23142316 · Publisher ↗
Neuregulin-1 (NRG-1) signaling regulates neuronal development, migration, myelination, and synaptic maintenance. Three members of tyrosine kinase receptor (Trk) family, TrkA, TrkB, and TrkC, have been identified in DRG n...
Neuregulin-1 (NRG-1) signaling regulates neuronal development, migration, myelination, and synaptic maintenance. Three members of tyrosine kinase receptor (Trk) family, TrkA, TrkB, and TrkC, have been identified in DRG neurons. Whether NRG-1β and its signaling pathways influence the expression of these Trk receptors in DRG neurons is still unclear. In the present study, primary cultured DRG neurons were used to determine the effects of NRG-1β on TrkA, TrkB, and TrkC expression in DRG neurons with excitotoxicity induced by glutamate (Glu). The involvement of phosphatidylinositol 3-kinase (PI3K)/Akt and the effects of extracellular signal-regulated protein kinase (ERK1/2) signaling pathways on NRG-1β were also determined. DRG neurons were cultured for 48h and then exposed to Glu, Glu plus NRG-1β, LY294002 plus Glu plus NRG-1β, PD98059 plus Glu plus NRG-1β, and PD98059 plus LY294002 plus Glu plus NRG-1β for an additional 24h. The DRG neurons were continuously exposed to culture media as a control. After that, all cultures were processed for detection of mRNA levels of TrkA, TrkB, and TrkC using real time-PCR analysis. Protein levels of TrkA, TrkB, and TrkC were detected using a Western blot assay. The expression of TrkA, TrkB, and TrkC in situ was determined by a fluorescent labeling technique. The levels of phosphorylated Akt (pAkt), phosphorylated ERK1/2 (pERK1/2), total protein levels of Akt and ERK1/2 were detected using a Western blot assay. The results indicated that in primary cultured DRG neurons with excitotoxicity induced by Glu, NRG-1β increased the expression of TrkA and TrkB their mRNAs, but not TrkC and its mRNA. Inhibitors (LY294002, PD98059) either alone or in combination blocked the effects of NRG-1β. NRG-1β may play an important role in regulating the expression of different Trk receptors in DRG neurons through the PI3K/Akt and ERK1/2 signaling pathways.
Critical residues in the transmembrane helical bundle domains of the human motilin receptor for erythromycin binding and activity.
Utsunomiya S, Matsuura B, Ueda T … +7 more , Miyake T, Furukawa S, Kumagi T, Ikeda Y, Abe M, Hiasa Y, Onji M
Regul Pept · 2013 Jan · PMID 23142315 · Publisher ↗
The motilin receptor belongs to a family of Class I G protein-coupled receptors, and is an important endogenous regulator of gastrointestinal motor function. Motilin and erythromycin, two chemically distinct full agonist...
The motilin receptor belongs to a family of Class I G protein-coupled receptors, and is an important endogenous regulator of gastrointestinal motor function. Motilin and erythromycin, two chemically distinct full agonists of the motilin receptor, are known to bind to distinct regions of this receptor, based on previous systematic mutagenesis of extracellular regions that dissociated the effects on these two agents. The action of these different chemical classes of agonists likely yields a common activation state of the cytosolic face of this receptor that is responsible for interaction with its G protein. In the current work, we studied the predicted transmembrane (TM) domains of this receptor for functional responses to motilin and erythromycin. Motilin receptor constructs were prepared in which each residue in the TM domains was mutated to alanine or valine. Each construct was expressed in COS cells and characterized for motilin and erythromycin binding and intracellular calcium responses stimulated by both agonists. Constructs with mutations of residues, Asp94, Leu95, Arg97 and Trp99 in TM2, Ser169 in TM4, and Tyr321 and Glu325 in TM6, were responsible for the negative impact on biological activity stimulated by erythromycin, but had no effect on motilin responses. On the other hand, constructs with mutations of residues, Leu113 in TM3, Pro172 in TM4, Trp250 and Tyr255 in TM5, and Gln334 in TM7, were negatively responsive to both erythromycin and motilin. These data support important roles of new regions in the TM domains of the motilin receptor for erythromycin action, suggesting differential mechanisms of actions by peptidyl and non-peptidyl ligands.
Ghrelin, leptin and insulin in cirrhotic children and adolescents: relationship with cirrhosis severity and nutritional status.
Dornelles CT, Goldani HA, Wilasco MI … +7 more , Maurer RL, Kieling CO, Porowski M, Ferreira CT, Santos JL, Vieira SM, Silveira TR
Regul Pept · 2013 Jan · PMID 23142314 · Publisher ↗
OBJECTIVE: Ghrelin, leptin, and insulin concentrations are involved in the control of food intake and they seem to be associated with anorexia-cachexia in cirrhotic patients. The present study aimed to investigate the re...
OBJECTIVE: Ghrelin, leptin, and insulin concentrations are involved in the control of food intake and they seem to be associated with anorexia-cachexia in cirrhotic patients. The present study aimed to investigate the relationship between the nutritional status and fasting ghrelin, leptin and insulin concentrations in pediatric cirrhotic patients. METHODS: Thirty-nine patients with cirrhosis and 39 healthy controls aged 0-15 years matched by sex and age were enrolled. Severity of liver disease was assessed by Child-Pugh classification, and Pediatric for End Stage Liver Disease (PELD) or Model for End-stage Liver Disease (MELD) scores. Blood samples were collected from patients and controls to assay total ghrelin, acyl ghrelin, leptin and insulin by using a commercial ELISA kit. Anthropometry parameters used were standard deviation score of height-for-age and triceps skinfold thickness-for-age ratio. A multiple linear regression analysis was used to determine the correlation between dependent and independent variables. RESULTS: Acyl ghrelin was significantly lower in cirrhotic patients than in controls [142 (93-278) pg/mL vs 275 (208-481) pg/mL, P=0.001]. After multiple linear regression analysis, total ghrelin and acyl ghrelin showed an inverse correlation with age; acyl ghrelin was associated with the severity of cirrhosis and des-acyl ghrelin with PELD or MELD scores ≥15. Leptin was positively correlated with gender and anthropometric parameters. Insulin was not associated with any variable. CONCLUSION: Low acyl ghrelin and high des-acyl ghrelin concentrations were associated with cirrhosis severity, whereas low leptin concentration was associated with undernourishment in children and adolescents with cirrhosis.
Insights into the impact of phenolic residue incorporation at each position along secretin for receptor binding and biological activity.
Dong M, Pinon DI, Miller LJ
Regul Pept · 2013 Jan · PMID 23142313 · Full text
Understanding of the structural importance of each position along a peptide ligand can provide important insights into the molecular basis for its receptor binding and biological activity. This has typically been evaluat...
Understanding of the structural importance of each position along a peptide ligand can provide important insights into the molecular basis for its receptor binding and biological activity. This has typically been evaluated using serial replacement of each natural residue with an alanine. In the current report, we have further complemented alanine scanning data with the serial replacement of each residue within secretin-27, the natural ligand for the prototypic class B G protein-coupled secretin receptor, using a photolabile phenolic residue. This not only provided the opportunity to probe spatial approximations between positions along a docked ligand with its receptor, but also provided structure-activity insights when compared with tolerance for alanine replacement of the same residues. The pattern of sensitivity to phenolic residue replacement was periodic within the carboxyl-terminal region of this peptide ligand, corresponding with alanine replacements in that region. This was supportive of the alpha-helical conformation of the peptide in that region and its docking within a groove in the receptor amino-terminal domain. In contrast, the pattern of sensitivity to phenolic residue replacement was almost continuous in the amino-terminal region of this peptide ligand, again similar to alanine replacements, however, there were key positions in which either the phenolic residue or alanine was differentially preferred. This provided insights into the receptor environment of the portion of this ligand most critical for its biological activity. As the structure of the intact receptor is elucidated, these data will provide a guide for ligand docking to the core domain and to help clarify the molecular basis of receptor activation.
Neurotransmissions of antidepressant-like effects of kisspeptin-13.
Tanaka M, Csabafi K, Telegdy G
Regul Pept · 2013 Jan · PMID 22999921 · Publisher ↗
Kisspeptins are G protein-coupled receptor ligands originally identified as human metastasis suppressor gene products that have the ability to suppress melanoma and breast cancer metastasis and which have recently been f...
Kisspeptins are G protein-coupled receptor ligands originally identified as human metastasis suppressor gene products that have the ability to suppress melanoma and breast cancer metastasis and which have recently been found to play an important role in initiating the secretion of gonadotropin-releasing hormone at puberty. In the brain, the gene is transcribed within the hippocampal dentate gyrus. Kisspeptin-13, one of the endogenous isoforms, consists of 13 amino acids. In this work, antidepressant-like effects of kisspeptin-13 were studied and the potential involvement of the adrenergic, serotonergic, cholinergic, dopaminergic and gabaergic receptors in its antidepressant-like effects was investigated in a modified forced swimming test (FST) in mice. The mice were pretreated with a nonselective α-adrenergic receptor antagonist, phenoxybenzamine, an α(1)/α(2β)-adrenergic receptor antagonist, prazosin, an α(2)-adrenergic receptor antagonist, yohimbine, a β-adrenergic receptor antagonist, propranolol, a mixed 5-HT(1)/5-HT(2) serotonergic receptor antagonist, methysergide, a nonselective 5-HT(2) serotonergic receptor antagonist, cyproheptadine, a nonselective muscarinic acetylcholine receptor antagonist, atropine, a D(2),D(3),D(4) dopamine receptor antagonist, haloperidol, or a γ-aminobutyric acid subunit A receptor antagonist, bicuculline. The FST revealed that kisspeptin-13 reversed the immobility, climbing and swimming times, suggesting antidepressant-like effects. Phenoxybenzamine, yohimbine and cyproheptadine prevented the effects of kisspeptin-13 on the immobility, climbing and swimming times, whereas prazosin, propranolol, methysergide, atropine, haloperidol and bicuculline did not modify the effects of kisspeptin-13. The results demonstrated that the antidepressant-like effects of kisspeptin-13 in a modified mouse FST are mediated, at least in part, by an interaction of the α(2)-adrenergic and 5-HT(2) serotonergic receptors.
Glucagon-like peptide-1 (GLP-1) receptor agonism or DPP-4 inhibition does not accelerate neoplasia in carcinogen treated mice.
Kissow H, Hartmann B, Holst JJ … +5 more , Viby NE, Hansen LS, Rosenkilde MM, Hare KJ, Poulsen SS
Regul Pept · 2012 Nov · PMID 22989472 · Publisher ↗
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel from the intestinal endocrine cells after nutrient intake. GLP-1 is an incretin hormone and analogues are availab...
INTRODUCTION: Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are secreted in parallel from the intestinal endocrine cells after nutrient intake. GLP-1 is an incretin hormone and analogues are available for the treatment of type 2 diabetes mellitus (T2DM). GLP-2 is an intestinal growth hormone and is shown to promote growth of colonic adenomas in carcinogen treated mice. Both peptides are degraded by dipeptidyl peptidase-4 (DPP-4) into inactive metabolites. DPP-4 inhibitors are therefore also in use for treatment of T2DM. It is possible that DPP-4 inhibition by enhancing the exposure of endogenous GLP-2 to the intestinal epithelia also might mediate growth and promote neoplasia. We investigated the intestinal growth effect of the GLP-1 receptor agonists (GLP-1 RAs) (liraglutide and exenatide) and DPP-4 inhibition (sitagliptin) in healthy mice. We also investigated the potential tumour promoting effect of liraglutide and sitaglitin in the colon of carcinogen treated mice. We used GLP-2 as a positive control. METHODS: For the growth study we treated healthy CD1 mice with liraglutide (300 μg×2), exenatide (12.5 μg×2) or vehicle subcutaneously and sitagliptin (8mg×2) or water by oral gavage for 10 or 30 days. We measured intestinal weight, cross sectional area, villus height and crypt depth. For the tumour study we treated carcinogen treated mice (1,2 dimethylhydrazine 21 mg/kg/week for 12 weeks) with liraglutide (300 μg×2), Gly2-GLP-2 (25 μg×2) or vehicle subcutaneously and sitagliptin (8 mg×2) or water by oral gavage for 45 days. We counted aberrant crypt foci (ACF), mucin depleted foci (MDF) and adenomas in the colon. Using COS-7 cells transfected with a GLP-2 receptor, we tested if liraglutide or exenatide could activate the receptor. RESULTS: In the 10 days experiment the relative small intestinal weight was increased with 56% in the liraglutide group (p<0.001) and 26% in the exenatide group (p<01) compared with vehicle treated mice. After 30 days of treatment, liraglutide did also increase the colonic weight (p<0.01). By morphometry the growth pattern mimicked that of GLP-2. Sitagliptin treatment had only a minor effect. In the carcinogen treated mice we found no increase of ACF in any of the groups, the numbers of MDF and adenomas after liraglutide and sitagliptin treatments were similar to their respective control groups. Neither liraglutide nor exenatide stimulated cAMP release from GLP-2 receptor transfected cells. CONCLUSION: Both GLP-1 analogues were potent growth stimulators of the healthy mouse intestine. No agonism was found for GLP-1 RAs at the GLP-2 receptor. Despite of the growth effect, liraglutide did not promote dysplasia in the colon. Sitagliptin did not show any tumour promoting effects, and non considerable growth effects.
Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis.
Erin N, Duymuş O, Oztürk S … +1 more , Demir N
Regul Pept · 2012 Nov · PMID 22982142 · Publisher ↗
Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated ma...
Chronic inflammation is involved in initiation as well as in progression of cancer. Semapimod, a tetravalent guanylhydrazon and formerly known as CNI-1493, inhibits the release of inflammatory cytokines from activated macrophages and this effect is partly mediated by the vagus nerve. Our previous findings demonstrated that inactivation of vagus nerve activity as well sensory neurons enhanced visceral metastasis of 4THM breast carcinoma. Hence semapimod by activating vagus nerve may inhibit breast cancer metastasis. Here, effects of semapimod on breast cancer metastasis, the role of vagal sensory neurons on this effect and changes in mediators of the neuroimmune connection, such as substance P (SP) as well as neprilysin-like activity, were examined. Vagotomy was performed on half of the control animals that were treated with semapimod following orthotopic injection of 4THM breast carcinoma cells. Semapimod decreased lung and liver metastases in control but not in vagotomized animals with an associated increased SP levels in sensory nerve endings. Semapimod also increased neprilysin-like activity in lung tissue of control animals but not in tumor-bearing animals. This is the first report demonstrating that semapimod enhances vagal sensory nerve activity and may have anti-tumoral effects under in-vivo conditions. Further studies, however, are required to elucidate the conditions and the mechanisms involved in anti-tumoral effects of semapimod.
Arterial stiffness and novel biomarkers in patients with abdominal aortic aneurysms.
Kadoglou NP, Papadakis I, Moulakakis KG … +7 more , Ikonomidis I, Alepaki M, Moustardas P, Lampropoulos S, Karakitsos P, Lekakis J, Liapis CD
Regul Pept · 2012 Nov · PMID 22982141 · Publisher ↗
OBJECTIVES: Pulse wave velocity (PWV) constitutes a valid index of arterial stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established vascular calcification inhibitors, highly correlated with infla...
OBJECTIVES: Pulse wave velocity (PWV) constitutes a valid index of arterial stiffness osteoprotegerin (OPG) and osteopontin (OPN) which are well-established vascular calcification inhibitors, highly correlated with inflammation, and cardiovascular events incidence. We investigated the association of PWV with the aforementioned novel biomarkers in patients with abdominal aortic aneurysm (AAA). METHODS: We enrolled 108 men with AAA (AAA group) candidates for endovascular repair. We excluded patients with Marfan syndrome or other collagen-related disorders. Forty-one age-matched men, with stable coronary artery disease (CAD), but without AAA, served as controls (CO group). PWV, clinical parameters and serum levels of osteoprotegerin (OPG), osteopontin (OPN), interleukin-6 (IL-6) and IL-10 were determined. RESULTS: With the exception of higher smoking rate and the lower statin's usage in the AAA group, there were non-significant differences in the rest of demographic and clinical parameters (p>0.05). We found significantly higher levels of PWV in AAA than CO group (12.99±3.75 m/s vs 10.03±1.57 m/s, p<0.001). In parallel, serum OPG, OPN, IL-6 levels were considerably increased, while IL-10 levels were downregulated (p<0.001) in AAA group. PWV positively correlated with mean blood pressure, OPG concentrations and AAA diameter in univariate and multivariate analysis (R(2)=0.498, p=0.008). Finally, age and OPG remained independent determinants of AAA presence in the whole study cohort. CONCLUSIONS: Arterial stiffness, circulating vascular calcification inhibitors and inflammatory mediators seem to be significantly upregulated in patients with AAA. An independent association of PWV with mean blood pressure, OPG and AAA diameter is of clinical importance which requires further investigation.
Tibolone has anti-inflammatory effects in estrogen-deficient female rats on the natriuretic peptide system and TNF-alpha.
de Medeiros AR, Lamas AZ, Caliman IF … +7 more , Dalpiaz PL, Firmes LB, de Abreu GR, Moysés MR, Lemos EM, dos Reis AM, Bissoli NS
Regul Pept · 2012 Nov · PMID 22975659 · Publisher ↗
Cardiovascular and immune system abnormalities have been reported in females with estrogen deficiency. To control these disorders in post-menopausal women, hormone replacement therapy (HRT) has been used. Tibolone has be...
Cardiovascular and immune system abnormalities have been reported in females with estrogen deficiency. To control these disorders in post-menopausal women, hormone replacement therapy (HRT) has been used. Tibolone has been used as a HRT, but the effects of tibolone on the natriuretic peptide system have not been determined. We investigated the effects of tibolone on the natriuretic peptide system and pro-inflammatory cytokines in ovariectomized (OVX) rats. Female rats were divided into four groups: SHAM, OVX, OVX treated with 17β-estradiol (OVX+E: 14 days) and OVX treated with tibolone (OVX+T: 14 days) beginning 21 days after ovariectomy. On day 35, blood was collected to determine atrial natriuretic peptide (ANP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. In addition, tissues were collected for determining ANP, natriuretic peptide receptor type-A (NPR-A), and NPR type-C (NPR-C) gene expression levels by RT-PCR. The cytokine levels of both IL-6 and TNF-α were increased in OVX animals. In comparison, IL-6 and TNF-α levels were reduced in OVX+E animals. TNF-α levels were reduced similarly in OVX+T animals, but IL-6 levels remained elevated in this group. The concentrations of ANP in the left atrium tissue and plasma were decreased after ovariectomy, as were ANP mRNA levels in the left atrium and NPR-A mRNA levels in kidney. No variation in NPR-C gene expression in the kidney tissue was observed among the groups. Tibolone and 17β-estradiol effectively increased plasma ANP and ANP mRNA levels in the left atrium, but did not normalize renal NPR-A levels. Since HRT with tibolone normalizes plasma ANP and serum TNF-alpha levels our results suggest that treatment with tibolone has anti-inflammatory effects and could prevent cardiovascular disease in the long-term.
An inhibitor of leukotriene synthesis affects vasopressin secretion following osmotic stimulus in rats.
dos Santos JF, de Oliveira-Pelegrin GR, Athayde LA … +1 more , da Rocha MJ
Regul Pept · 2012 Nov · PMID 22960410 · Publisher ↗
Previous studies revealed the presence of LTC(4) synthase in paraventricular vasopressinergic neurons, suggesting a role for leukotrienes (LTs) in certain neuroendocrine system functions. Our aim was to study the effect...
Previous studies revealed the presence of LTC(4) synthase in paraventricular vasopressinergic neurons, suggesting a role for leukotrienes (LTs) in certain neuroendocrine system functions. Our aim was to study the effect of an inhibitor of LT synthesis in the release of arginine vasopressin (AVP) following an osmotic stimulus in rats. Male Wistar rats received an intra-cerebroventricular injection of 2 μl of the LT synthesis inhibitor MK-886 (1, 2, or 4 μg/kg), or vehicle (DMSO 5%), 1h before an intraperitoneal injection of hypertonic saline (NaCl 2M) or isotonic saline (NaCl 0.01 M) in a volume corresponding to 1% of body weight. Thirty minutes after the osmotic stimulus, the animals were decapitated and blood was collected for determining hematocrit, plasma osmolality and plasma AVP levels. As expected, the injection of hypertonic saline significantly increased (P<0.05) the hematocrit, plasma osmolality and plasma AVP levels. While inhibiting LT synthesis by central administration of MK-886 did not cause any additional increase in hematocrit or osmolality, plasma AVP levels were augmented (P<0.05). We conclude that central leukotrienes may have a modulatory role in AVP secretion following an osmotic stimulus, this deserving future studies.
Effects of trypsin, thrombin and proteinase-activated receptors on guinea pig common bile duct motility.
Huang SC
Regul Pept · 2012 Nov · PMID 22960409 · Publisher ↗
Trypsin and thrombin activate proteinase-activated receptors (PARs), which modulate gastrointestinal motility. The common bile duct is exposed to many proteinases that can activate PARs, especially during infection and s...
Trypsin and thrombin activate proteinase-activated receptors (PARs), which modulate gastrointestinal motility. The common bile duct is exposed to many proteinases that can activate PARs, especially during infection and stone obstruction. We investigated PAR effects on common bile duct motility in vitro. Contraction and relaxation of isolated guinea pig common bile duct strips caused by PAR(1), PAR(2) and PAR(4) agonists were measured using isometric transducers. Reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the expression of PAR(1) and PAR(2). Thrombin and two PAR(1) peptide agonists, TFLLR-NH(2) and SFLLRN-NH(2), evoked moderate relaxation of the carbachol-contracted common bile duct in a concentration-dependent manner. Trypsin and three PAR(2) peptide agonists, 2-furoyl-LIGRLO-NH(2), SLIGKV-NH(2) and SLIGRL-NH(2), generated moderate to marked relaxation as well. The existence of PAR(1) and PAR(2) mRNA in the common bile duct was identified by RT-PCR. Moreover, two PAR(4)-selective agonists, AYPGKF-NH(2) and GYPGQV-NH(2), produced relaxation of the common bile duct. In contrast, all PAR(1), PAR(2) and PAR(4) inactive control peptides did not elicit relaxation. This indicates that PAR(1), PAR(2) and PAR(4) mediate common bile duct relaxation. The thrombin, TFLLR-NH(2), trypsin, and AYPGKF-NH(2)-induced responses were not affected by tetrodotoxin, implying that the PAR effects are not neurally mediated. Our findings provide the first evidence that PAR(1) and PAR(2) mediate whereas agonists of PAR(4) elicit relaxation of the guinea pig common bile duct. Trypsin and thrombin relax the common bile duct. PARs may play an important role in the control of common bile duct motility.
Connective tissue growth factor level is increased in patients with liver cirrhosis but is not associated with complications or extent of liver injury.
Bauer S, Eisinger K, Wiest R … +5 more , Karrasch T, Scherer MN, Farkas S, Aslanidis C, Buechler C
Regul Pept · 2012 Nov · PMID 22960408 · Publisher ↗
Connective tissue growth factor (CTGF) is a profibrotic protein whose systemic levels are increased in liver cirrhosis. Here, association of CTGF with stages of liver injury and complications of cirrhotic liver disease h...
Connective tissue growth factor (CTGF) is a profibrotic protein whose systemic levels are increased in liver cirrhosis. Here, association of CTGF with stages of liver injury and complications of cirrhotic liver disease has been analyzed in patients with different aetiologies of hepatic injury. CTGF is significantly increased in portal venous serum (PVS), hepatic venous serum (HVS) and systemic venous serum (SVS) of 46 patients with liver cirrhosis compared to eight liver-healthy controls. In patients´ blood samples CTGF in HVS is about 6% higher than PVS levels indicating that CTGF produced in the liver is released to the circulation. CTGF is not associated with stages of liver cirrhosis defined by CHILD-PUGH or MELD score nor with secondary complications of portal hypertension (varices, ascites, spontaneous bacterial peritonitis). Transforming growth factor β (TGFβ) induces CTGF synthesis in hepatocytes and a positive association of systemic TGFβ1 and SVS and HVS CTGF is found. Three months after placing transjugular intrahepatic portosystemic shunt (TIPS) hepatic venous pressure gradient is reduced whereas CHILD-PUGH score, TGFβ1 and CTGF are not altered in serum of 15 patients. Current data show that the cirrhotic liver releases little CTGF but SVS, HVS and PVS CTGF levels are not associated with residual liver function and complications of cirrhosis.
Analgesic properties of chimeric peptide based on morphiceptin and PFRTic-amide.
Li M, Zhou L, Ma G … +1 more , Dong S
Regul Pept · 2012 Nov · PMID 22960407 · Publisher ↗
A chimeric opioid peptide (MCRT, YPFPFRTic-NH(2)) was here designed and synthesized. This peptide was based on morphiceptin (YPFP-NH(2)) and a neuropeptide FF (NPFF) derivative (PFRTic-NH(2)) sharing one proline. This pe...
A chimeric opioid peptide (MCRT, YPFPFRTic-NH(2)) was here designed and synthesized. This peptide was based on morphiceptin (YPFP-NH(2)) and a neuropeptide FF (NPFF) derivative (PFRTic-NH(2)) sharing one proline. This peptide is intended to produce potent analgesia. MCRT was found to induce analgesic activity in a dose- and time-dependent manner, as indicated by a tail flick latency test in mice to which it had been intracerebroventricularly administered (5-60 min, 0.025-2.5 nmol/kg (0.5-50 pmol per mouse), ED(50)=1.49 nmol/kg). At 2.5nmol/kg, MCRT showed significantly higher levels of analgesic activity than morphiceptin or PFR(Tic)amide at 2500 nmol/kg. Naltrindole and cyprodime were found to partially but significantly inhibit this analgesic activity, but naloxone blocked it completely. The kappa opioid receptor antagonist nor-BNI was found to slightly inhibit MCRT and morphiceptin. Pre-injection of BIBP3226 and co-administration of NPFF and MCRT showed that NPFF receptors were involved in the analgesia of MCRT. BIBP3226 was found to weaken the analgesic effects of MCRT, but BIBP3226 could not block the analgesic effects of PFR(Tic)amide. Overall, MCRT was found to have stronger analgesic activity than morphiceptin or PFR(Tic)amide when interacting with mixed μ/δ opioid receptor interactions. MCRT also showed partial interaction with NPFF receptors.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe