GABAergic inhibition of nitric oxide-mediated relaxation of guinea-pig ileum

The effects of GABA receptor agonists were investigated on guinea-pig isola ted ileum longitudinal muscle with intact myenteric plexus. Electrical fiel d stimulation (1 Hz, 10 s) of the histamine (1 mu M)-precontracted preparat ion caused 3 contraction followed by a relaxation. Relaxations were inhibit ed by L-N-G-nitro-arginine (L-NA; EC50 3 mu M) in a concentration-dependent manner. The inhibitory action of 10 mu M L-NA was blocked by 10 mu M L-arg inine but not by D-arginine, which indicates that the relaxation was largel y mediated by endogenous nitric oxide (NO). Tetrodotoxin (1 mu M) reduced t he relaxation only by about 50%. GABA and the GABA(B) agonist, baclofen, in hibited the field stimulation-induced longitudinal muscle relaxation in a c oncentration-dependent manner. The GABA(B) receptor antagonist, saclofen (1 0 mu M), antagonised the effect of baclofen (apparent pA(2) of saclofen: 5. 6). Muscimol (10 mu M) similarly inhibited the relaxation, and this inhibit ion was prevented by bicuculline (1 mu M). It is concluded that nitrergic n erves of the guinea-pig myenteric plexus are endowed with GABA(A) and GABA( B) receptors which mediate inhibition of NO release.