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Nitric oxide blocks bile canalicular contraction by inhibiting inositol trisphosphate-dependent calcium mobilization.
- Source :
-
Gastroenterology [Gastroenterology] 1995 Mar; Vol. 108 (3), pp. 841-9. - Publication Year :
- 1995
-
Abstract
- Background/aims: The biochemical mechanism of bile canalicular contraction is similar to that of smooth muscle contraction. Contraction follows inositol-1,4,5-trisphosphate (InsP3)-dependent Ca2+ release, which activates actin-myosin interactions. Nitric oxide is a myorelaxant through the actions of 5'-cyclic guanosine monophosphate (cGMP) and is produced in hepatocytes exposed to endotoxin and cytokines. The aim of this study was to investigate the effect of nitric oxide on canalicular contraction and to determine the mechanism by which cGMP interferes with the contractile signal.<br />Methods: The canalicular motility in rat hepatocyte doublets was measured by microscopic image analysis, and intracellular Ca2+ was measured by fluorescence microscopy. cGMP and InsP3 were determined by radio-immunoassay and high-pressure liquid chromatography. Ca2+ release from liver homogenate was measured by filtration and superfusion assays.<br />Results: Compounds that release nitric oxide stimulated hepatocellular production of cGMP and prevented agonist-induced contraction by inhibiting the increase in intracellular Ca2+. The cGMP analogue bromo-cGMP prevented contraction and the increase in Ca2+. Bromo-cGMP marginally decreased InsP3 production. cGMP blocked InsP3-dependent Ca2+ release from internal stores.<br />Conclusions: These findings suggest that nitric oxide interferes with Ca2+ signals by cGMP-mediated inhibition of the InsP3 receptor/Ca2+ channel and that hepatocellular production of nitric oxide may be cholestatic by impairing canalicular motility.
- Subjects :
- Animals
Cyclic GMP pharmacology
Male
Molsidomine analogs & derivatives
Molsidomine pharmacology
Nitroprusside pharmacology
Rats
Signal Transduction
Vasodilator Agents pharmacology
Bile Canaliculi drug effects
Calcium metabolism
Calcium Channel Blockers pharmacology
Inositol 1,4,5-Trisphosphate physiology
Muscle Contraction drug effects
Nitric Oxide pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0016-5085
- Volume :
- 108
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 7875487
- Full Text :
- https://doi.org/10.1016/0016-5085(95)90459-x