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

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 μM)-precontracted preparation caused a contraction followed by a relaxation. Relaxations were inhibited by l-N ^G-nitro-arginine (l-NA; EC₅₀ 3 μM) in a concentration-dependent manner. The inhibitory action of 10 μM l-NA was blocked by 10 μM l-arginine but not by d-arginine, which indicates that the relaxation was largely mediated by endogenous nitric oxide (NO). Tetrodotoxin (1 μM) 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 μM), antagonised the effect of baclofen (apparent pA ₂ of saclofen: 5.6). Muscimol (10 μM) similarly inhibited the relaxation, and this inhibition was prevented by bicuculline (1 μM). 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. Received: 5 February 1999 / Accepted: 22 March 1999