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

In the absence of ligands, G-protein coupled receptors interconvert between active and inactive conformations, These conformations are stabilized by agonists and antagonists, respectively, Like agonists, G-proteins are thought to preferentially associate with receptors in the active conformation and should therefore be able to promote their formation in the absence of agonist, We show that over-expression of G(q) induces constitutive activation of compatible muscarinic receptors and that this activity is blocked by muscarinic antagonists. G(q) also increases the potency and efficacy of agonists, These results indicate that regulation of G-protein levels has a profound impact on receptor control of cellular physiology, even in the absence of agonist ligands.