CONSTITUTIVE ACTIVATION OF MUSCARINIC RECEPTORS BY THE G-PROTEIN G(Q)

In the absence of ligands, G-protein coupled receptors interconvert be tween active and inactive conformations, These conformations are stabi lized by agonists and antagonists, respectively, Like agonists, G-prot eins are thought to preferentially associate with receptors in the act ive conformation and should therefore be able to promote their formati on in the absence of agonist, We show that over-expression of G(q) ind uces constitutive activation of compatible muscarinic receptors and th at this activity is blocked by muscarinic antagonists. G(q) also incre ases the potency and efficacy of agonists, These results indicate that regulation of G-protein levels has a profound impact on receptor cont rol of cellular physiology, even in the absence of agonist ligands.