Article: article from journal or magazin.
Constitutively active mutants of the beta1-adrenergic receptor.
We provide the first evidence that point mutations can constitutively activate the beta(1)-adrenergic receptor (AR). Leucine 322 of the beta(1)-AR in the C-terminal portion of its third intracellular loop was replaced with seven amino acids (I, 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.
Adrenergic beta-1 Receptor Agonists, Adrenergic beta-2 Receptor Agonists, Adrenergic beta-Agonists/metabolism, Adrenergic beta-Agonists/pharmacology, Adrenergic beta-Antagonists/metabolism, Adrenergic beta-Antagonists/pharmacology, Amino Acid Substitution, Betaxolol/metabolism, Betaxolol/pharmacology, Carbazoles/metabolism, Carbazoles/pharmacology, Cell Line/drug effects, Cell Line/metabolism, Cyclic AMP/metabolism, Epinephrine/metabolism, Epinephrine/pharmacology, Humans, Imidazoles/metabolism, Imidazoles/pharmacology, Isoproterenol/metabolism, Isoproterenol/pharmacology, Labetalol/metabolism, Labetalol/pharmacology, Point Mutation, Practolol/metabolism, Practolol/pharmacology, Propanolamines/metabolism, Propanolamines/pharmacology, Receptors, Adrenergic, beta-1/genetics, Receptors, Adrenergic, beta-1/metabolism, Receptors, Adrenergic, beta-2/metabolism, Recombinant Proteins/genetics, Recombinant Proteins/metabolism, Timolol/metabolism, Timolol/pharmacology
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