The action of amyl nitrite and isosorbide dinitrate on the contractility of sphincter of Oddi of guinea-pigs.
1. This study was designed to investigate whether relaxation of isolated guinea-pig sphincter of Oddi preparation by nitrates is mediated by guanylate cyclase activation indirectly by nitric oxide (NO), as in vascular tissues. 2. Sodium nitroprusside, isosorbide dinitrate and amyl nitrite induced dose-dependent relaxations of Oddi's sphincter precontracted by potassium chloride (150 mM). Methylene blue (5 x 10(-5) M), an inhibitor of guanylate cyclase, did not significantly inhibit the relaxations caused by nitrovasodilators. 3. Unlike potassium chloride, acetylcholine (10(-7) - 10(-3) M) induced unsustained contractions which were significantly increased by methylene blue. NG-monomethyl-L-arginine (L-NMMA; 4 x 10(-4) M), an inhibitor of NO biosynthesis, also increased the contractile response to acetylcholine. 4. These results suggest that another mechanism rather than inhibition of guanylate cyclase is involved in the nitrovasodilators-induced relaxations and that acetylcholine releases a relaxing factor, possibly NO, that may modulate its own contraction in this preparation.
Department of Pharmacology, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
F
F
Göcer
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E
Yaris
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Tuncer
D000109:Acetylcholine / Q000494:pharmacology; D000680:Amyl Nitrite / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D011189:Potassium Chloride / Q000494:pharmacology; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000502:physiology; D019323:omega-N-Methylarginine
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D011189:Potassium Chloride; D000680:Amyl Nitrite; D001120:Arginine; D007548:Isosorbide Dinitrate; D000109:Acetylcholine; D008751:Methylene Blue