Carbachol induces desensitization of cardiac beta-adrenergic receptors through muscarinic M1 receptors.

Incubation of enzymatically dissociated cardiac myocytes with carbachol leads to a time- and concentration-dependent loss of beta-receptors assayable with [3H]CGP-12177. This loss is due to a redistribution of beta-receptors from the plasma membrane to a cytosol-derived vesicular fraction, consistent with an internalization process. The carbachol effects are not influenced by gallamine or oxotremorine which interact with the high-affinity (M2) muscarinic receptors. These results suggest that carbachol-induced desensitization is secondary to activation of protein kinase C by diacylglycerols generated through M1 receptor-linked phosphoinositide hydrolysis.