CGP-35348 BLOCKS NORADRENALINE-RELEASE-INHIBITING GABA(B) RECEPTORS IN THE PIG RETINA, RAT VENA-CAVA AND PITHED RAT VASCULATURE

In superfused pig retina discs, preincubated with H-3-noradrenaline, t he electrically (3 Hz) evoked tritium overflow was inhibited by 7-amin obutyric acid (GABA) and the GABA(B) receptor agonist R-(-)-baclofen b ut was not affected by the GABA(A) receptor agonist 3-amino-1-propanes ulphonic acid. The effect of GABA was counteracted by the GABA(B) rece ptor antagonist CGP 35348 [P-(3-aminopropyl)-P-diethoxymethylphosphini c acid] but was not influenced by the GABA(A) receptor antagonist SR 9 5531 oxypropyl)-3-amino-6-paramethoxyphenylpyridazinium bromide]. Furt hermore, CGP 35348 antagonized the inhibitory effect of R-(-)-baclofen on the electrically (0.66 Hz) evoked tritium overflow in superfused r at vena cava segments, preincubated with H-3-noradrenaline, and on the electrically (0.5 Hz) induced rise in diastolic blood pressure in pit hed rats. The present results suggest that GABA is capable of inhibiti ng noradrenaline release (most likely from vascular sympathetic nerve endings) in the pig retina via GABA(B) receptors and that CGP 35348 is a valuable tool for the characterization of GABA(B) receptors in vitr o and in situ.