Assessment of a ternary model for the binding of agonists to neurohumoral receptors.
A frequently cited variant of the "mobile receptor" hypothesis has been examined for its ability to describe the binding of agonists at neurohumoral receptors that operate via a guanylyl nucleotide binding protein. The model involves a reversible association between the receptor (R) and the G protein (G). Agonists (A) bind with different affinity to R and to the RG complex; similarly, G differentiates between R and the AR complex. Theoretical binding curves calculated according to the model have been analyzed in terms of the Hill equation and as a mixture of independent and noninteracting sites. The model is shown to be compatible in some respects with reported data on the binding of agonists to the beta-adrenergic receptor but not to the muscarinic cholinergic or D2 dopaminergic receptors. It is difficult to reconcile with the reported effects of guanylyl nucleotides, magnesium, and N-ethylmaleimide on the binding of agonists at any neurohumoral receptor.
D000818:Animals; D001665:Binding Sites; D019204:GTP-Binding Proteins / Q000378:metabolism; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000378:metabolism*
D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D019204:GTP-Binding Proteins