Propylbenzilylcholine mustard-sensitive and -resistant muscarinic receptors in cardiac muscle.
1. A left atrium of guinea pig driven electrically was used as a test organ containing M2-cholinoceptors. 2. Concentration-response curves of carbachol and butyltrimethylammonium, muscarinic full agonists, were progressively inhibited by 10 and 30 min treatments of the atrium with propylbenzilylcholine mustard (PrBCM; 10(-6) M). The 50 min treatment with PrBCM had no further significant inhibitory effect on their curves. 3. The 30 min treatment of the atrium with PrBCM completely inhibited the concentration-response curve of pilocarpine, a partial agonist. In the atrium after the 30 min treatment with PrBCM, pilocarpine shifted the concentration-response curves of the full agonists, suggesting a competitive antagonism. 4. These results suggest an existence of two subtypes of M2-receptors; PrBCM-sensitive and -resistant ones, and that the full agonists inhibit the twitch through an interaction of both the receptors, while the partial agonist produce inhibition through an activation of PrBCM-sensitive ones.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
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Takayanagi
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Koike
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Saito
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D004351:Drug Resistance; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism; D010862:Pilocarpine / Q000494:pharmacology; D011438:Propylbenzilylcholine Mustard / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects*
D000644:Quaternary Ammonium Compounds; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D011438:Propylbenzilylcholine Mustard; C071455:1-butyltrimethylammonium; D002217:Carbachol