Positive inotropic effects induced by carbachol in rat atria treated with islet-activating protein (IAP)--association with phosphatidylinositol breakdown.
1. To elucidate the functional consequences of phosphatidyl inositol (PI) breakdown produced by activation of the muscarinic receptor of the atrial muscle, and to clarify the subtypes of the muscarinic receptor involved, the effects of muscarinic agonists and antagonists on mechanical function were studied in atria isolated from rats given intravenous islet-activating protein (IAP; 50 micrograms kg-1 body weight) 48-72 h before the experiments. 2. The negative chronotropic and inotropic actions of carbachol (CCh) were attenuated and positive inotropic effects (62.5 +/- 5.8% above basal level) were observed with 10(-5) -10(-3) M CCh. Oxotremorine did not produce positive inotropic effects even in doses as high as 3 x 10(-4) M High doses of carbachol produced positive chronotropic effects, although the effects were weak. 3. Propranolol (10(-7) M) did not modify the positive inotropic effect of carbachol observed in IAP-treated atria, nor was there any change in the tissue cyclic AMP levels after carbachol. 4. High doses (10(-5)-10(-3) M) of carbachol produced PI breakdown in the absence and presence of IAP. Oxotremorine (3 x 10(-4) M) did not produce PI breakdown. In the presence of oxotremorine, the positive inotropic effects and PI breakdown by carbachol were abolished. 5. The positive inotropic effect of carbachol was readily antagonized by atropine but pirenzepine and gallamine exhibited only weak antagonist effects. 6. These results suggest that a muscarinic agonist such as carbachol can produce a positive inotropic effect in IAP-treated atria, in association with PI breakdown, through activation of a muscarinic receptor which shows some similarity to that previously identified in smooth muscles.
Imai
S
S
Department of Pharmacology, Niigata University School of Medicine, Japan.
Ohta
H
H
D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006325:Heart Atria / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D002316:Cardiotonic Agents; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D010566:Virulence Factors, Bordetella; D002217:Carbachol; D037342:Pertussis Toxin