Prostaglandin synthesis elicited by cholinergic stimuli is mediated by activation of M2 muscarinic receptors in rabbit heart.
This study was performed to determine the subtype of muscarinic receptors involved in the action of cholinergic stimuli on prostaglandin (PG) synthesis in the isolated rabbit heart perfused at a constant flow rate with Krebs Hanseleit buffer. Acetylcholine (ACh, 1.0-10.0 nmol), an M1 and M2 receptor agonist, and arecaidine propargyl ester (APE, 1.0-5.0 nmol), a selective M2 agonist, produced a dose-related increase in the output of 6-keto-PGF1 alpha and a decrease in heart rate, whereas 4-[m-chlorophenyl carbamoyl]-2-butynyl-trimethylammonium chloride (McN-A-343, 10 nmol-1.0 mumol), a selective M1 receptor agonist, did not alter PG output. The increase in PG output or the decrease in heart rate elicited by ACh or APE was abolished by atropine (0.1 microM), an M1 and M2 receptor antagonist, and by 11-[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5, 11-dihydro-6-H-pyrido-[2,3-b] [1,4]-benzodiazepine-6-one (AF-DX-116, 1.0 microM), a selective M2 antagonist, but not by pirenzepine (1.0 microM), a selective M1 antagonist. The developed tension, which was also reduced by ACh and APE, but not by McN-A-343, was minimized by AF-DX-116 and not by lower concentrations of pirenzepine that attenuated the coronary vasodilator effect of McN-A-343. Lower doses of ACh (1.0-5.0 nmol) caused coronary vasodilation, whereas higher doses of ACh (10.0 nmol) and lower as well as higher doses of APE produced a biphasic effect--an initial vasodilation followed by vasoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)
D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology; D001115:Arecoline / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000378:metabolism*
D001095:Arachidonic Acids; D006584:Hexamethonium Compounds; D011453:Prostaglandins; D011976:Receptors, Muscarinic; C015000:arecaidine esters; D016718:Arachidonic Acid; D010890:Pirenzepine; D001115:Arecoline; D008455:(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethylammonium Chloride; D011433:Propranolol; D000109:Acetylcholine; C048593:otenzepad; D007213:Indomethacin; D010646:Phentolamine