Constitutively active mutants of the beta1-adrenergic receptor

FEBS Lett. 1999 Sep 3;457(3):302-6. doi: 10.1016/s0014-5793(99)01064-9.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Carvedilol
  • 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

Substances

  • Adrenergic beta-1 Receptor Agonists
  • Adrenergic beta-2 Receptor Agonists
  • Adrenergic beta-Agonists
  • Adrenergic beta-Antagonists
  • Carbazoles
  • Imidazoles
  • Propanolamines
  • Receptors, Adrenergic, beta-1
  • Receptors, Adrenergic, beta-2
  • Recombinant Proteins
  • Carvedilol
  • ICI 118551
  • Timolol
  • CGP 20712A
  • Cyclic AMP
  • Isoproterenol
  • Betaxolol
  • Labetalol
  • Practolol
  • Epinephrine