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Background/Aims: Recent evidence supports a predominant role of β3-adrenoceptors at the end of pregnancy in myometrium. This study was designed to characterize the pharmacology of the selective β3-adrenoceptor agonist CL 316243 on oxytocin-induced myometrial contractions and the levels of cAMP and cGMP of myometrial strips isolated from term-pregnant rats. Methods: Myometrial strips were obtained from term-pregnant Wistar albino rats (n = 10), mounted in organ baths and tested for changes in isometric tension in response to CL 316243 (10-10-10-5M) on oxytocin-induced myometrial contractions. Effects of CL 316243 on cAMP and cGMP levels in isolated myometrial strips (n = 8) were evaluated by radioimmunoassay kits. We evaluated the effect of increasing concentrations of CL 316243 on myometrial contractions and on contractions of myometrial smooth muscle pretreated with metoprolol, ICI 118.551 and SR 59230A (β1-, β2-, β3-adrenoceptor antagonists, respectively, 10-6M). Results: The inhibition of the amplitude of oxytocin-induced contractions by CL 316243 were antagonized with SR 59230A (10-6M), but they were not changed by metoprolol (10-6M) or ICI 118.551 (10-6M). CL 316243 increased cAMP levels compared to the control group. CL 316243 increased cGMP levels, in the CL 316243 group more than in the control group, but this increase is less significant than cAMP levels. Conclusion: These results demonstrate that the inhibition of rat myometrial contractions with CL 316243 is mediated by β3-adrenoceptor subtype and increased cAMP and cGMP levels. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to investigate the effects of peritonitis on spontaneous contractions of ileum and jejunum smooth muscles isolated from rats. Peritonitis was induced by cecal ligation and puncture in 8 rats. Another group of 8 rats underwent a sham operation and acted as controls. Twenty-four hours after the operation, the rats were killed, and their ileum and jejunum smooth muscles were excised and placed in circular muscle direction in a 10 ml organ bath. Changes in the amplitude and frequency of spontaneous contractions were analyzed before and after the addition of different antagonists. Peritonitis induced the decrease in the amplitude and frequency of spontaneous contractions in ileum and jejunum smooth muscles. In control groups, both ileum and jejunum, the amplitude and frequency of spontaneous contractions were significantly elevated in the presence of N G-nitro-l-arginine (l-NNA) and indomethacin. In peritonitis groups, both ileum and jejunum, the amplitude and frequency of spontaneous contractions were significantly enhanced in the presence of l-NNA, aminoguanidine, indomethacin and celecoxib compared to control values. In conclusion, peritonitis induces the decrease in the amplitude and frequency of spontaneous contractions of ileum and jejunum that can be attributed to the rise of nitric oxide synthase and cyclooxygenase isoforms levels. [Copyright &y& Elsevier]

Background: The mechanisms involved in the impaired gallbladder contractile response in peritonitis are unknown. The aim of this study was to determine the effect of peritonitis on the contraction and relaxation responses to different agonists in gallbladder smooth muscle in guinea pig.Materials and methods: Peritonitis was induced by cecal ligation and puncture (CLP) in 10 guinea pigs. Another group of 10 guinea pigs underwent a sham operation and acted as controls. Twenty-four hours after the operation, the guinea pigs were killed, and gallbladder strips were placed in organ bath. The contraction responses to KCl, carbachol, and histamine, and relaxation responses to cyclooxygenase inhibitors (indomethacin, nimesulide, and DFU) on KCl-induced contractions were recorded.Results: There was no significant difference between the contractile responsiveness to KCl, but maximum contractile responses (Emax) to carbachol and histamine were significantly reduced. Indomethacin, nimesulide, and DFU concentration dependently inhibited on KCl-induced contractions of gallbladder smooth muscle. Emax values of indomethacin, nimesulide, and DFU were significantly reduced in the peritonitis group compared with controls (P < 0.05). The inhibitor effects of nimesulide and DFU were considerably similar, but inhibitor effect of indomethacin was significantly less than that measured for nimesulide and DFU in both control and peritonitis groups (P < 0.05).Conclusions: The contraction responses to carbachol and histamine and relaxation responses to COX inhibitors on gallbladder smooth muscle are significantly decreased by peritonitis. Although the mechanism of the decrease in contraction and relaxation responses in CLP-induced peritonitis is completely unknown, we speculate that impaired smooth muscle responses may be related to an alteration in the regulation of receptor/postreceptor excitation-response coupling and/or through changes on Ca2+ influx. [Copyright &y& Elsevier]

Aim: The aim of this study is to investigate whether nitric oxide (NO)-mediated colonic motility was altered in rat irritable bowel syndrome (IBS) model, using different isoforms of NO-synthase (NOS) inhibitors. Materials and Methods: The animal model of IBS-like visceral hypersensitivity was induced by intra-colonic infusion of 0.5% acetic acid (AA) in saline once daily from postnatal days 8 to 21. Control animals received saline instead of AA. Experiments were performed at the end of 8 weeks. Distal colon tissues were resected and direct effects of different NOS inhibitors; N-omega-nitro-L-arginine methyl ester hydrochloride, (L-NAME), ARL-17477 dihydrochloride hydrate (ARL 17477), N-[[3-(Aminomethyl) phenyl] methyl]-ethanimidamidedihydrochloride (1400 W), and N5-(1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO) were evaluated concentration-dependently in vitro tissue bath. Besides, morphology of both groups was assessed with hematoxylin and eosin (H and E) staining and the impact of NO antibodies was determined using the immunohistochemical method. Results: The mean pressure values of spontaneous contractions and KCL (80 mmol/L) responses of distal colonic segments were similar in normal and IBS rats. L-NAME and ARL-17477 significantly increased the mean pressure of spontaneous colonic contractions in normal rats versus own base values (P < 0.05), but this increase did not significantly different when compared to IBS rats. In H and E staining, there was no difference with regard to morphology between two groups. Neuronal NOS (nNOS) immunoreactivity was found to be significantly decreased in IBS when compared to control groups (P < 0.05). Conclusion: L-NAME and ARL-17477 mediated mean pressure values were found to be slightly decreased in IBS rats. These findings may be related to a decrease in nNOS level in IBS. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the effects of nimesulide and pentoxifylline on the contractile effects of KCl, carbachol and substance P in the longitudinal muscle of rat ileum during peritonitis. Peritonitis was induced in rat ileum by cecal ligation and puncture. Thirty rats were operated on to induce peritonitis, 10 of which received nimesulide (5 mg/kg, subcutaneously) and 10 of which received pentoxifylline (25 mg/kg, subcutaneously) before the operation; 10 other rats underwent a sham operation and acted as controls. Twenty-four hours after the operation, ileum segments were transferred to isolated organ baths and responses to KCl, carbachol and substance P were recorded. Emax values of KCl, carbachol and substance P were markedly lower (P<0.05), with no change in the pD2 values, in the peritonitis group than in the controls. Peritonitis-induced changes in the KCl, carbachol and substance P responses of ileum were significantly restored by nimesulide (P<0.05), but not by pentoxifylline. The improved contractile responses following nimesulide treatment indicate that products of cyclooxygenase-II may be, at least in part, responsible for the decreased contractile responses to KCl, carbachol and substance P in peritonitis. [Copyright &y& Elsevier]

To the best of our knowledge this is the first case report describing exposure to varenicline, an a4ß2 nicotinic acetylcholine partial receptor agonist used for smoking cessation therapy in pregnancy. A 29-year-old multiparous woman with an unplanned pregnancy has used varenicline 2 mg/day unintentionally yet regularly 4 weeks from her last menstrual period. Fetal ultrasound performed at each trimester, detailed anomaly scan, and fetal echocardiography which were performed at the 22nd gestational week showed normal fetal growth with no malformations. The patient delivered a healthy baby at the 38th week of gestation with normal Apgar score and physical examination findings. Age-appropriate physical and neurological development of the child has been observed for 6 months. Although it is not possible to draw definitive conclusions, this case report may contribute to the current available limited data regarding the safety of varenicline use in pregnancy. [ABSTRACT FROM AUTHOR]