Indications for selective coupling to phosphoinositide hydrolysis or to adenylate cyclase inhibition by endogenous muscarinic receptor subtypes M3 and M4 but not by M2 in tumor cell lines.

The muscarinic receptor subtype mRNAs expressed in cell lines were determined by Northern blot analysis. The biochemical responses of the muscarinic receptors in these cell lines (phosphoinositide hydrolysis and cAMP levels) were studied and correlated to the corresponding muscarinic receptor subtype as determined by mRNA expression. PC12 cells that expressed M4 subtype mRNA exhibited muscarinically dependent adenylate cyclase inhibition, whereas C6 and SK-N-SH cells expressing M3 subtype mRNA exhibited muscarinically dependent phosphoinositide hydrolysis. IMR-32 cells (M2 subtype mRNA) exhibited both muscarinically dependent phosphoinositide hydrolysis and adenylate cyclase inhibition. These results suggest that endogenous M3 and M4 receptor subtypes are selectively coupled to phosphoinositide hydrolysis and adenylate cyclase inhibition, respectively, whereas the M2 receptor subtype is coupled to both responses.