Down-regulation and desensitization of the muscarinic M1 and M2 receptors in transfected fibroblast B82 cells.

Murine fibroblast cell lines stably transfected with the rat muscarinic m1 or m2 receptor genes were used to study the homologous regulation of the muscarinic M1 or M2 receptors. The cells were pretreated with the muscarinic receptor agonists, (+)-cismethyl-dioxolane, carbachol, 2,8-dimethyl-3-methylene-1-oxa-8-aza-spiro- [4,5]decane ((+) or (-)-YM796) or the muscarinic receptor antagonist atropine for up to 24 h. Our study has demonstrated that the muscarinic receptor nonselective full agonist, (+)-cismethyl-dioxolane, induced the down-regulation of both the muscarinic M1 and the M2 receptors in association with desensitization of the receptor-mediated functions. The muscarinic M1 receptors are down-regulated without significant receptor internalization while the muscarinic M2 receptors are more sensitive to down-regulation than the muscarinic M1 receptors because of significant internalization of the muscarinic M2 receptors in our system. The muscarinic M1 receptor partial agonist, (-)-YM796 induced less down-regulation and no significant desensitization of the muscarinic M1 receptors with no substantial effect on the muscarinic M2 receptor density or function.