title: Reciprocal modulation of agonist and antagonist binding to muscarinic cholinergic receptor by guanine nucleotide.
abstract: The ability of guanine nucleotide to decrease the binding affinity of agonists but not antagonists has been documented in a number of hormone and neurotransmitter receptor systems. By contrast, recent reports indicate that both agonist and antagonist binding to the muscarinic cholinergic receptors appear to be regulated in a reciprocal fashion by guanine nucleotide. We document two forms of the muscarinic cholinergic receptor in frog heart, which are present in approximately equal proportions and which display high-agonist/low antagonist and low-agonist/high-antagonist affinities, respectively. Guanine nucleotide appears to convert the former type of site into the latter type. These observations can be interpreted in terms of a model for two 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.
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006165:Guanylyl Imidodiphosphate / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010276:Parasympatholytics / Q000378:metabolism; D010277:Parasympathomimetics / Q000378:metabolism; D011894:Rana pipiens; D011950:Receptors, Cholinergic / Q000187:drug effects*; D011976:Receptors, Muscarinic / Q000187:drug effects*
chemical_list: D006150:Guanine Nucleotides; D010276:Parasympatholytics; D010277:Parasympathomimetics; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D006165:Guanylyl Imidodiphosphate