DEVELOPMENTAL STUDIES ON CHOLINERGIC MU CARINIC RECEPTORS

Abstract

This study illustrates the lack of intrinsic activity of SR

95639A in activating muscarinic receptor-mediated second messenger signals. This was demonsterated in muscarinic receptor-coupled responses in cell lines transfected with the genes of M1 and M3 receptors, in addition to responses induced by neuronal M1 , M2 , M3 or M4 muscarinic receptors. Thus, our results do not confirm any apparent muscarinic agonistic activity for this compound. Furthermore, they do not show marked selectivity of the compound among muscarinic receptor subtypes at the level of ligand recognition site. Also, activation of striatal muscarinic receptors linked to neurotransmitters release with muscarinic agonists depends on the intrinsic activity and affinity state of such agonists. This was demonsterated in rat striatal muscarfnic receptors coupled to either inhibition of. choline release or potentiation of dopamine release. The results demonstrate that, oxotremorine differentiates between·striatal muscarinic receptors linked to both systems as it was a partial agonist at M4 receptor subtype having low affinity for this receptor subtype and a full

agonist· with high affinity for M2• The full agonists methacholine . and carbamylcholine had high affinities for both subtypes. Also, pilocarpine and McN-A-343 bind to both subtypes with only low affinities.