ACCELERATED COMMUNICATION Influence of G Protein Type on Agonist Efficacy

An agonist at a specific G protein-coupled receptor may exhibit a range of efficacies for any given response in a cell-specific manner. We report that the relationship between different states of agonism is regulated by the type of G protein ex-pressed in the cell. In NIH-3T3 a2-adrenergic receptor (AR) transfectants, the a2-AR agonists clonidine, oxymetazoline, UK-14304, and epinephrine increased [35S]guanosine-59-O-(3-thio)triphosphate binding in a dose-dependent manner from a basal value of 101.2 6 6.5 fmol/mg to a maximal response (100 mM) of 196.6 6 9.8, 182.3 6 2, 328.1 6 11.2, and 340.6 6 3 fmol/mg, respectively. Thus, clonidine and oxymetazoline be-haved as partial agonists. Receptor-mediated activation of G proteins in membrane preparations was blocked by cell pre-treatment with pertussis toxin, indicating receptor coupling t