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

ABSTRACT

The effects of GABA receptor agonists were investigated on guinea-pig isolated ileum longitudinal muscle with intact myenteric plexus. Electrical field stimulation (1 Hz, 10 s) of the histamine (1 microM)-precontracted preparation caused a contraction followed by a relaxation. Relaxations were inhibited by L-N(G)-nitroarginine (L-NA; EC50 3 microM) in a concentration-dependent manner. The inhibitory action of 10 microM L-NA was blocked by 10 microM L-arginine but not by D-arginine, which indicates that the relaxation was largely mediated by endogenous nitric oxide (NO). Tetrodotoxin (1 microM) reduced the relaxation only by about 50%. GABA and the GABA(B) agonist, baclofen, inhibited the field stimulation-induced longitudinal muscle relaxation in a concentration-dependent manner. The GABA(B) receptor antagonist, saclofen (10 microM), antagonised the effect of baclofen (apparent pA2 of saclofen 5.6). Muscimol (10 microM) similarly inhibited the relaxation, and this inhibition was prevented by bicuculline (1 microM). It is concluded that nitrergic nerves of the guinea-pig myenteric plexus are endowed with GABA(A) and GABA(B) receptors which mediate inhibition of NO release.