A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents

Science. 1992 Aug 14;257(5072):977-80. doi: 10.1126/science.1354394.

Abstract

The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents. An aspartic acid residue (Asp79) highly conserved among guanine nucleotide-binding protein (G protein)-coupled receptors was mutated to asparagine; in cells transfected with the mutant alpha 2-receptor, agonists inhibited adenylyl cyclase and calcium currents but did not increase potassium currents. Because distinct G proteins appear to couple adrenoceptors to potassium and calcium currents, the present findings suggest that the mutant alpha 2-adrenoceptor cannot achieve the conformation necessary to activate G proteins that mediate potassium channel activation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic alpha-Agonists / pharmacology
  • Animals
  • Asparagine
  • Aspartic Acid
  • Brimonidine Tartrate
  • Calcium Channels / drug effects
  • Calcium Channels / metabolism
  • Calcium Channels / physiology*
  • Cell Line
  • Clonidine / pharmacology
  • GTP-Binding Proteins / metabolism
  • Membrane Potentials / drug effects
  • Mutagenesis, Site-Directed*
  • Potassium Channels / drug effects
  • Potassium Channels / metabolism
  • Potassium Channels / physiology*
  • Quinoxalines / pharmacology
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism
  • Receptors, Adrenergic, alpha / physiology*
  • Receptors, Neurotransmitter / drug effects
  • Receptors, Neurotransmitter / physiology*
  • Receptors, Somatostatin
  • Recombinant Proteins / drug effects
  • Recombinant Proteins / metabolism
  • Somatostatin / metabolism
  • Somatostatin / pharmacology
  • Transfection

Substances

  • Adrenergic alpha-Agonists
  • Calcium Channels
  • Potassium Channels
  • Quinoxalines
  • Receptors, Adrenergic, alpha
  • Receptors, Neurotransmitter
  • Receptors, Somatostatin
  • Recombinant Proteins
  • Aspartic Acid
  • Brimonidine Tartrate
  • Somatostatin
  • Asparagine
  • GTP-Binding Proteins
  • Clonidine