Potentiation of monovalent cation effects on ligand binding to cardiac muscarinic receptors in N-ethylmaleimide treated membranes.
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.
D000641:Ammonia / Q000494:pharmacology; D000818:Animals; D002414:Cations, Monovalent / Q000494:pharmacology*; D002642:Chick Embryo; D004357:Drug Synergism; D005033:Ethylmaleimide / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D011813:Quinuclidinyl Benzilate / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000378:metabolism*
D002414:Cations, Monovalent; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate; D010095:Oxotremorine; D011813:Quinuclidinyl Benzilate; D000641:Ammonia; D005033:Ethylmaleimide