Alkylation of the bovine anterior pituitary D2-dopamine receptor: inconsistency with predictions of the ternary complex model.
The ability of a high affinity, N-chloroethyl derivative to irreversibly occupy dopamine receptors has been used to probe the nature of the interaction of the bovine anterior pituitary D2-dopamine receptor with a putative G-protein. Conditions were developed that resulted in a significant 40-60% decrease in the total D2-dopamine receptor concentration without affecting the affinity of the receptor for either antagonists or agonists. Computer analyses of radioligand binding data for the pituitary D2-dopamine receptor have indicated that consistent with the decrease in total receptor concentration following alkylation there was a comparable decrease in the apparent agonist high-affinity state of the receptor as modelled according to independent classes of binding sites. These data were not consistent with the predictions of the ternary complex model. These results indicate that the present form of the model is not sufficient to account fully for the mechanism of ligand interactions with the pituitary D2-dopamine receptor and suggest, furthermore, that the receptor and the G-protein might be considered as a complex where ligand binding to either component regulates ligand interactions of the other, rather than enhancing the degree of association of the components.
D000478:Alkylation; D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003198:Computer Simulation; D018492:Dopamine Antagonists; D005476:Fluphenazine / Q000031:analogs & derivatives* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008024:Ligands; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship
D018492:Dopamine Antagonists; D008024:Ligands; D011954:Receptors, Dopamine; D013134:Spiperone; C009074:N-n-propylnorapomorphine; C053619:fluphenazine-N-mustard; D019204:GTP-Binding Proteins; D001058:Apomorphine; D005476:Fluphenazine