The cloned murine M₁ muscarinic receptor is associated with the hydrolysis of phosphatidylinositols in transfected murine B82 cells

A rat genomic DNA clone was isolated by its homology with a conserved primary sequence among the mammalian and avian beta adrenergic and procine muscarinic receptors. A gene identified in this clone was highly homologous to the rat M₁ muscarinic receptor. Stable expression of this gene was achieved in an established murine fibroblast cell line, B82. The gene product exhibits M₁ type muscarinic receptor characteristics, as it has high affinity for PZ but low affinity for AF-DX 116. Carbachol stimulated the hydrolysis of phosphatidylinositols in the transfected cells. Pirenzepine had a more potent inhibitory effect on this response than AF-DX 116 since their functional inhibition constants were 13 nM and 480 nM, respectively, which is consistent with an M₁ pharmacological profile. These data suggest that the M₁ muscarinic receptor encoded by the gene is coupled to the hydrolysis of phosphatidylinositols after transfecting this gene into the B82 cells.