Open AccessReciprocal modulation of agonist and antagonist binding to muscarinic cholinergic receptor by guanine nucleotide.
Author(s) -
Ernst Bürgisser,
André De Léan,
Robert J. Lefkowitz
Publication year - 1982
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.79.6.1732
Subject(s) - agonist , competitive antagonist , muscarinic antagonist , neurotransmitter receptor , guanine , agonist antagonist , chemistry , antagonist , muscarinic acetylcholine receptor , muscarinic acetylcholine receptor m1 , muscarinic acetylcholine receptor m4 , receptor , biology , endocrinology , biochemistry , nucleotide , gene
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.