McMahon_1983_Biochem.Biophys.Res.Commun_111_41

Guanine nucleotides and monovalent cations decrease the affinity of cardiac muscarinic receptors for agonists and are required for muscarinic receptor mediated inhibition of adenylate cyclase. N-ethylmaleimide abolished the effects of Gpp(NH)p on the ability of the agonist oxotremorine to inhibit the binding of the antagonist [3H]quinuclidinyl benzilate to purified chick heart membranes. However, the effects of NH4+ to decrease the IC50 for oxotremorine were retained in N-ethylmaleimide treated membranes. The N-ethylmaleimide treatment mimicked the effects of Gpp(NH)p and the oxotremorine inhibition curves obtained with treated membranes in the presence of NH4+ were identical to those obtained in control membranes in the presence of NH4+ and Gpp(NH)p. The results suggest that monovalent cation effects on muscarinic receptors are mediated at a site distinct from effects produced by guanine nucleotides and are greater on free receptors than on receptors coupled to guanine nucleotide binding proteins.