Interaction of muscarinic drugs with their receptor.
Interaction of muscarinic drugs with their receptor was studied in the logitudinal muscle of guinea pig ileum. The pD2-value, the index for agonistic activity of a partial agonist was practically equal to its pA2-value, the index for competitive antagonistic activity and to its pKA-value which was a negative logarithm of a dissociation constant (KA), suggesting that the muscarinic drugs such as full and partial agonists and a competitive antagonist interacted with one binding site in the muscarinic receptor. Effects of a GTP-analogue, Gpp(NH)p (guanyl-5'-y limidodiphosphate) decreased affinities of full and partial agonists to the muscarinic receptor in a manner that was correlated with their efficacies. A relationship between the Hill's coefficients of the muscarinic drugs and their efficacies suggest that the ability to distinguish the agonist binding sites was related to their efficacy.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010277:Parasympathomimetics / Q000378:metabolism* / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D010277:Parasympathomimetics; D000644:Quaternary Ammonium Compounds; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; D011813:Quinuclidinyl Benzilate; D001285:Atropine; D002217:Carbachol