Release of acetylcholine mediated by cholecystokinin receptor from the guinea pig sphincter of Oddi.
Mechanisms involved in the action of cholecystokinin octapeptide (CCK-8) on the isolated circular muscle of the guinea pig sphincter of Oddi were investigated. CCK-8 (10(-9) to 10(-6) M) caused a concentration-dependent contraction of the sphincter. Angiotensin II, bethanechol and serotonin also contracted this tissue. CCK-8 exerted the most potent effect. However, bradykinin, porcine motilin and norepinephrine failed to elicit any contraction. The CCK-8-induced contraction was inhibited by about 60% by atropine (3 X 10(-7) M) or tetrodotoxin (3 X 10(-7) M) but was not affected by hexamethonium (3 X 10(-5) to 10(-4) M) or phentolamine (3 X 10(-6) to 10(-5) M). Proglumide (3 X 10(-4) to 3 X 10(-3) M), a derivative of glutaramic acid, inhibited competitively the contraction by CCK-8. However, proglumide influenced neither the electrically elicited twitch contraction nor the bethanechol-induced contraction. CCK-8 evoked a concentration-related release of [3H]acetylcholine (ACh) from previously labeled stores. The CCK-8-evoked release of [3H]ACh was eliminated by tetrodotoxin and was inhibited, in a concentration-dependent manner, by proglumide. These results suggest that the contractile response to CCK-8 of the guinea pig sphincter of Oddi consists of a direct effect on the smooth muscle and an indirect effect mediated by ACh release from postganglionic parasympathetic neurons.
D000109:Acetylcholine / Q000378:metabolism*; D014670:Ampulla of Vater / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002794:Choline / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D006859:Hydrogen / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011377:Proglumide / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D012701:Serotonin / Q000494:pharmacology; D012844:Sincalide / Q000494:pharmacology; D009803:Sphincter of Oddi / Q000187:drug effects / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D001626:Bethanechol Compounds; D006584:Hexamethonium Compounds; D011949:Receptors, Cholecystokinin; D018723:Bethanechol; D000804:Angiotensin II; D012701:Serotonin; D018738:Hexamethonium; D013779:Tetrodotoxin; D001285:Atropine; D006859:Hydrogen; D011377:Proglumide; D012844:Sincalide; D002794:Choline; D000109:Acetylcholine; D001920:Bradykinin; D010646:Phentolamine