Tonic activation of presynaptic GABA(B) receptors in the opener neuromuscular junction of crayfish

Release of excitatory transmitter from boutons on crayfrsh nerve terminals was inhibited by (R,S)-baclofen, an agonist at GABA(B) receptors. Baclofen had no postsynaptic actions as it reduced quantal content without affecting quantal amplitude, The effect of baclofen increased with concentration pro ducing 18% inhibition at 10 mu M EC50, 50% inhibition at 30 mu M; maximal i nhibition, 85% at 100 mu M and higher. There was no desensitization. even w ith 200 or 320 mu M baclofen. Phaclofen, an antagonist at GABA(B) receptors , competitively antagonized the inhibitory action of baclofen (K-D = 50 mu M, equivalent to a pA(2) = 4.3 +/- 0.1). Phaclofen on its own at concentrat ions below 200 mu M had no effect on release, whereas at 200 mu M phaclofen itself increased the control level of release by 60%, as did 2-hydroxy-sac lofen (200 mu M), another antagonist at GABA(B) receptors. This increase wa s evidently due to antagonism of a persistent level of GABA in the synaptic cleft, since the effect was abolished by destruction of the presynaptic in hibitory fiber, using intra-axonal pronase; We conclude that presynaptic GA BA(B) receptors, with a pharmacological profile similar to that of mammalia n GABA(B) receptors, are involved in the control of transmitter release at the crayfish neuromuscular junction.