GABA, GLUTAMATE AND SUBSTANCE P-LIKE IMMUNOREACTIVITY RELEASE - EFFECTS OF NOVEL GABA(B) ANTAGONISTS

1 The effects of various GABA receptor ligands on the electrically-evo ked release of endogenous GABA, glutamate and substance P-like immunor eactivity from the dorsal horn of rat isolated spinal cord were examin ed. 2 Exogenous GABA (10-300 mu M) significantly decreased the evoked, but not basal, release of endogenous glutamate in a concentration-dep endent manner. The GABA(A) agonist, isoguvacine (1-100 mu M), failed t o decrease the release of glutamate although it did reduce the release of GABA. Baclofen (0.1-1000 mu M), the GABA(B) agonist, reduced the r elease of GABA and glutamate in a stereospecific and concentration-dep endent manner. 3 The actions of five GABA(B) antagonists on these rele ase systems were compared. CGP36742, CGP52432, CGP55845A and CGP57250A significantly increased the evoked release of GABA and glutamate. The y also reversed the effects of (-)-baclofen in a concentration-depende nt manner. On the other hand, while CGP56999A had no effect on glutama te release, it was an effective antagonist of the baclofen-induced inh ibition of GABA and substance P release. 4 These results suggest that GABA(B) receptors on nerve terminals within the dorsal horn spinal cor d may be heterogeneous. However, this is based solely on the data obta ined with CGP56999A which affected only GABA and substance P, but not glutamate, release.