Cholinergic and GABAergic regulation of nitric oxide synthesis in the guinea pig ileum.
Nitric oxide (NO) synthesis was examined in intact longitudinal muscle-myenteric plexus preparations of the guinea pig ileum by determining the formation of [3H]citrulline during incubation with [3H]arginine. Spontaneous [3H]citrulline production after 30 min was 80-90 dpm/mg, which constituted approximately 1% of the tissue radioactivity. Electrical stimulation (10 Hz) led to a threefold increase in [3H]citrulline formation. Removal of calcium from the medium or addition of NG-nitro-L-arginine strongly inhibited both spontaneous and electrically induced production of [3H]citrulline. TTX reduced the electrically induced but not spontaneous [3H]citrulline formation. The electrically induced formation of [3H]citrulline was diminished by (+)-tubocurarine and mecamylamine and enhanced by scopolamine, which suggests that endogenous ACh inhibits, via muscarinic receptors, and stimulates, via nicotinic receptors, the NO synthesis in the myenteric plexus. The GABAA receptor agonist muscimol and GABA also reduced the electrically evoked formation of [3H]citrulline, whereas baclofen was without effect. Bicuculline antagonized the inhibitory effect of GABA. It is concluded that nitrergic myenteric neurons are equipped with GABAA receptors, which mediate inhibition of NO synthesis.
Hebeiss
K
K
Department of Pharmacology, University of Mainz, D-55101 Mainz, Germany.
Kilbinger
H
H
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018679:Cholinergic Agonists / Q000494:pharmacology*; D018680:Cholinergic Antagonists / Q000494:pharmacology*; D002956:Citrulline / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D009118:Muscimol / Q000494:pharmacology; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009197:Myenteric Plexus / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology*; D010095:Oxotremorine / Q000494:pharmacology; D012601:Scopolamine / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D018679:Cholinergic Agonists; D018680:Cholinergic Antagonists; D018755:GABA Agonists; D019335:Nitroarginine; D009118:Muscimol; D002956:Citrulline; D009569:Nitric Oxide; D013779:Tetrodotoxin; D004533:Egtazic Acid; D005680:gamma-Aminobutyric Acid; D010095:Oxotremorine; D008464:Mecamylamine; D012601:Scopolamine; D001418:Baclofen; D014403:Tubocurarine; D001640:Bicuculline