CGP 35348 blocks noradrenaline-release-inhibiting GABAB receptors in the pig retina, rat vena cava and pithed rat vasculature

Pharmacology. 1993 Aug;47(2):111-6. doi: 10.1159/000139085.

Abstract

In superfused pig retina discs, preincubated with 3H-noradrenaline, the electrically (3 Hz) evoked tritium overflow was inhibited by gamma-aminobutyric acid (GABA) and the GABAB receptor agonist R-(-)-baclofen but was not affected by the GABAA receptor agonist 3-amino-1-propanesulphonic acid. The effect of GABA was counteracted by the GABAB receptor antagonist CGP 35348 [P-(3-aminopropyl)-P-diethoxymethylphosphinic acid] but was not influenced by the GABAA receptor antagonist SR 95531 [2-(3-carboxypropyl)-3-amino-6-paramethoxyphenylpyridazinium bromide]. Furthermore, CGP 35348 antagonized the inhibitory effect of R-(-)-baclofen on the electrically (0.66 Hz) evoked tritium overflow in superfused rat vena cava segments, preincubated with 3H-noradrenaline, and on the electrically (0.5 Hz) induced rise in diastolic blood pressure in pithed rats. The present results suggest that GABA is capable of inhibiting noradrenaline release (most likely from vascular sympathetic nerve endings) in the pig retina via GABAB receptors and that CGP 35348 is a valuable tool for the characterization of GABAB receptors in vitro and in situ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Blood Pressure / drug effects
  • Blood Vessels / drug effects*
  • Decerebrate State
  • Dose-Response Relationship, Drug
  • In Vitro Techniques
  • Norepinephrine / antagonists & inhibitors*
  • Organophosphorus Compounds / pharmacology*
  • Pyridazines / pharmacology
  • Rats
  • Receptors, GABA-A / drug effects*
  • Retina / drug effects*
  • Swine
  • Venae Cavae / drug effects*

Substances

  • Organophosphorus Compounds
  • Pyridazines
  • Receptors, GABA-A
  • CGP 35348
  • gabazine
  • Baclofen
  • Norepinephrine