Influence of indomethacin on effects of endothelin-1 on guinea pig isolated rings of common bile duct and sphincter of Oddi.
The effects of endothelin-1 on motility of guinea pig extra-hepatic biliary tract portions were studied. Endothelin-1 (< or =100 nM) failed to contract rings of hepatic, cystic, proximal or distal common bile ducts, or choledochal or papillary halves of sphincter of Oddi. At 100 nM, endothelin-1 or sarafotoxin S6c (selective endothelin ET(B) receptor agonist) inhibited contractions of choledochal (but not papillary) sphincter of Oddi to carbachol (1 microM) by 63+/-5 and 45+/-9%, respectively. In distal common bile duct, indomethacin (5.6 microM) unmasked potent contractile effects of endothelin-1 [EC(50) 7.8 (5.5-11.1) nM; E(MAX) 80+/-6% of response to 80 mM KCl] and enhanced the contractile potency of carbachol (585-fold at EC(50) level), but not cholecystokinin C-terminal octapeptide. Inhibition of cholinergic responsiveness of the choledochal sphincter of Oddi by endothelin-1 was reduced by BQ-123 (1 microM; endothelin ET(A) receptor antagonist; cyclo[DTrp-DAsp-Pro-DVal-Leu]) and abolished by either BQ-123 plus BQ-788 (1 microM; endothelin ET(B) receptor antagonist; N-cis-2,6-dimethylpiperidinocarbonyl-L-gamma-methylleucyl-D-1-methoxycarboyl-D-norleucine) or indomethacin. Thus, eicosanoids of the cyclo-oxygenase pathway (i.e. prostanoids) suppress endothelin-1-induced contractions of distal common bile duct and mediate endothelin ET(A) and ET(B) receptor-dependent inhibition of cholinergic responsiveness of the choledochal portion of the sphincter of Oddi.
Koepp
Janice
J
Department of Pharmacology, CCB, Biological Sciences Centre, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, 88015-420, Florianópolis, SC, Brazil.
Cardozo
Alcíbia M
AM
D'Orléans-Juste
Pedro
P
Rae
Giles A
GA
D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology; D003135:Common Bile Duct / Q000187:drug effects / Q000502:physiology; D003549:Cystic Duct / Q000187:drug effects / Q000502:physiology; D004347:Drug Interactions; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006500:Hepatic Duct, Common / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology*; D008297:Male; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000502:physiology
D002317:Cardiovascular Agents; D019332:Endothelin-1; D007213:Indomethacin