Up-regulation of GABA(B) receptors by chronic administration of the GABA(B) receptor antagonist SCH 50,911

Eur J Pharmacol. 2005 May 16;515(1-3):94-8. doi: 10.1016/j.ejphar.2005.03.040.

Abstract

Chronic treatment of mice with the specific gamma-aminobutyric acid(B) (GABA(B)) receptor antagonist (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50,911) increased both the number of GABA(B) receptors in the whole brain (measured as [3H]CGP 54626 [S-(R,R)]-3-[[1-(3,4-dichlorophenyl)amino]-2-hydroxypropyl](cyclohexylmethyl)phosphinic acid hydrochloride binding) and the ability of baclofen to activate GABA(B) receptor coupled G-protein (measured as % reduction of the EC50 of baclofen to activate [35S]GTP(gamma)S binding). The results indicate that persistent blockade of GABA(B) receptors leads to their compensatory up-regulation and suggest that GABA(B) receptors are tonically activated by endogenous GABA.

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Binding, Competitive / drug effects
  • Brain / drug effects
  • Brain / metabolism
  • Dose-Response Relationship, Drug
  • GABA Agonists / pharmacology
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
  • Male
  • Mice
  • Mice, Inbred DBA
  • Morpholines / pharmacology*
  • Organophosphorus Compounds / metabolism
  • Receptors, GABA-B / metabolism*
  • Sulfur Radioisotopes
  • Tritium
  • Up-Regulation

Substances

  • (+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid
  • GABA Agonists
  • GABA-B Receptor Agonists
  • GABA-B Receptor Antagonists
  • Morpholines
  • Organophosphorus Compounds
  • Receptors, GABA-B
  • Sulfur Radioisotopes
  • Tritium
  • CGP 54626
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • Baclofen