Reciprocal modulation of agonist and antagonist binding to muscarinic cholinergic receptor by guanine nucleotide.

Abstract

Both agonist and antagonist binding to the muscarinic cholinergic receptors are apparently regulated in a reciprocal fashion by guanine nucleotide. Two forms of the muscarinic cholinergic receptor in frog [Rana pipiens] heart, which are present in approximately equal proportions and which display high-agonist/low antagonist and low-agonist/high-antagonist affinities, respectively, were documented. Guanine nucleotide apparently converts the former type of site into the latter type. These observations can be interpreted in terms of a model for 2 interconvertible forms of the muscarinic cholinergic receptor reciprocally favored by agonists and antagonists. This model has implications both for the understanding of neurotransmitter-receptor interactions generally and for the nature of the biological effects of receptor antagonists.