Effect of M2 muscarinic receptor antagonist 4-DAMP, on prostaglandin synthesis and mechanical function in the isolated rabbit heart.
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.
Jaiswal
N
N
Department of Pharmacology, College of Medicine, University of Tennessee, Memphis 38163.
Lambrecht
G
G
Mutschler
E
E
Malik
K U
KU
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004347:Drug Interactions; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology
D010276:Parasympatholytics; D010277:Parasympathomimetics; D010880:Piperidines; D011453:Prostaglandins; D011976:Receptors, Muscarinic; C042375:4-diphenylacetoxy-1,1-dimethylpiperidinium