Constitutively active mutants of the β1-adrenergic receptor

We provide the first evidence that point mutations can constitutively activate the beta(1)-adrenergic receptor (AR), Leucine 322 of the Pi-AR in the C-terminal portion of its third intracellular loop was replaced,vith seven amino acids CI, T, E, F, C, A and K) differing in their physico-chemical properties. The beta(1)-AR mutants expressed in HEK-293 cells displayed various levels of constitutive activity which could be partially inhibited by some beta-blockers. The results of this study might have interesting implications for future studies aiming at elucidating the activation process of the beta(1)-AR as well as the mechanism of action of beta-blockers. (C) 1999 Federation of European Biochemical Societies.