Jaiswal_1989_Gen.Pharmacol_20_497

1. Muscarinic agonist acetylcholine (ACh) (non-selective) and arecaidine propargyl ester (APE) (M2 selective agonist) produced a increase in the output of 6-keto PGF1 alpha and a decrease in the heart rate and myocardial developed tension in a dose-dependent manner. 2. 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. 3. The increase in 6-keto PGF1 alpha output elicited by 3 nmol of ACh or APE was inhibited by 10 nM of classical muscarinic receptor antagonist atropine or by the selective M2 beta muscarinic receptor antagonist 4-(diphenylacetoxy-N-methyl piperidine) methiodide (4-DAMP). 4. The decrease in heart rate and myocardial developed tension produced by ACh and APE was attenuated by atropine and 4-DAMP. The coronary vasodilator effect of ACh and APE and the vasoconstrictor effect of APE were also attenuated by both of these muscarinic antagonists.