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.