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 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.
Kilbinger
H
H
Pharmakologisches Institut der Universität Mainz, Germany.
Ginap
T
T
Erbelding
D
D
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D004791:Enzyme Inhibitors; D018755:GABA Agonists; D058785:GABA-A Receptor Agonists; D058786:GABA-B Receptor Agonists; D019335:Nitroarginine; D009118:Muscimol; D009569:Nitric Oxide; D013779:Tetrodotoxin; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D001640:Bicuculline