The alpha9 nicotinic acetylcholine receptor shares pharmacological properties with type A gamma-aminobutyric acid, glycine, and type 3 serotonin receptors

Mol Pharmacol. 1999 Feb;55(2):248-54. doi: 10.1124/mol.55.2.248.

Abstract

In the present study, we provide evidence that the alpha9 nicotinic acetylcholine receptor (nAChR) shares pharmacological properties with members of the Cys-loop family of receptors. Thus, the type A gamma-aminobutyric acid receptor antagonist bicuculline, the glycinergic antagonist strychnine, and the type 3 serotonin receptor antagonist ICS-205,930 block ACh-evoked currents in alpha9-injected Xenopus laevis oocytes with the following rank order of potency: strychnine > ICS-205,930 > bicuculline. Block by antagonists was reflected in an increase in the acetylcholine (ACh) EC50 value, with no changes in agonist maximal response or Hill coefficient, which suggests a competitive type of block. Moreover, whereas neither gamma-aminobutyric acid nor glycine modified ACh-evoked currents, serotonin blocked responses to ACh in a concentration-dependent manner. The present results suggest that the alpha9 nAChR must conserve in its primary structure some residues responsible for ligand binding common to other Cys-loop receptors. In addition, it adds further evidence that the alpha9 nAChR and the cholinergic receptor present at the base of cochlear outer hair cells have similar pharmacological properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Animals
  • Barium / pharmacology
  • Bicuculline / pharmacology
  • Calcium / metabolism
  • Chelating Agents / pharmacology
  • DNA, Complementary / genetics
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Female
  • GABA Antagonists / pharmacology
  • Glycine / pharmacology
  • Glycine Agents / pharmacology
  • Indoles / pharmacology
  • Membrane Potentials / drug effects
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Receptors, GABA-A / metabolism*
  • Receptors, Glycine / metabolism*
  • Receptors, Nicotinic / genetics
  • Receptors, Nicotinic / metabolism*
  • Receptors, Serotonin / metabolism*
  • Receptors, Serotonin, 5-HT3
  • Recombinant Fusion Proteins / drug effects
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Strychnine / pharmacology
  • Tropisetron
  • Xenopus laevis

Substances

  • Chelating Agents
  • DNA, Complementary
  • GABA Antagonists
  • Glycine Agents
  • Indoles
  • Receptors, GABA-A
  • Receptors, Glycine
  • Receptors, Nicotinic
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT3
  • Recombinant Fusion Proteins
  • Serotonin Antagonists
  • Indo-1 pentaacetoxymethyl ester
  • Barium
  • Serotonin
  • Egtazic Acid
  • Tropisetron
  • Strychnine
  • 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid
  • Acetylcholine
  • Calcium
  • Glycine
  • Bicuculline