Selective iNOS inhibition enhances spontaneous gallbladder motility in the Australian possum
| Autor: | Per Sandström, Michael Michael, Charmaine M. Woods, James Toouli, Molly Bond, Gino T.P. Saccone, Joar Svanvik |
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| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Pathology Gallbladder Emptying Physiology Gene Expression Nitric Oxide Synthase Type II Motility Biology Polymerase Chain Reaction Nitric oxide Contractility chemistry.chemical_compound Organ Culture Techniques In vivo Internal medicine Cholecystitis medicine Animals RNA Messenger Enzyme Inhibitors Endocrine and Autonomic Systems Gallbladder Gastroenterology medicine.disease Nitric oxide synthase Endocrinology medicine.anatomical_structure chemistry Quinazolines biology.protein Female Trichosurus |
| Zdroj: | Neurogastroenterology & Motility. 19:497-503 |
| ISSN: | 1365-2982 1350-1925 |
| Popis: | Gallbladder inflammation is a common and painful disease. Inducible nitric oxide synthase (iNOS) plays a major role in inflammatory diseases, and iNOS inhibitors are being developed as therapeutic agents. Reports are inconsistent regarding iNOS expression in normal gallbladder. The aim of this study was to determine the effect of iNOS inhibition on spontaneous gallbladder motility. mRNA extracted from normal possum gallbladders was analysed by PCR. Gallbladder contractility was evaluated using a highly selective iNOS inhibitor AR-C102222AA (AR-C) in in vitro muscle strips (0.1-10 000 microm) and in vivo (0.1-30 micromol kg(-1)) experiments. Gene expression analysis revealed the presence of iNOS mRNA in normal gallbladder (n = 3). In vitro, AR-C (0.1-1000 micromol L(-1)) produced a concentration-dependent increase in spontaneous gallbladder contractile activity and basal tension (P < 0.05; n = 6). The maximum effect was a 1.8-fold increase in activity and 2.1-fold increase in basal tension. Pretreatment of muscle strips with tetrodotoxin (1 micromol L(-1)) did not block the AR-C-induced response (n = 5). In vivo, AR-C (30 micromol kg(-1), i.v.) increased gallbladder contraction frequency (P < 0.05; n = 8). These data suggest that iNOS is continually expressed in the normal gallbladder, which presumably releases low levels of nitric oxide and in turn may modulate spontaneous gallbladder motility. AR-C may be a beneficial treatment for patients suffering from acute cholecystitis. |
| Databáze: | OpenAIRE |
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