Presynaptic muscarinic and alpha-adrenoceptor-mediated regulation of GABA release from myenteric neurones of the guinea-pig small intestine.
The effects of cholinomimetic and sympathomimetic drugs on the release of [3H]-gamma-aminobutyric acid ([3H]-GABA) evoked by high K+ from the isolated small intestine of the guinea-pig were investigated, in the presence of tetrodotoxin. Acetylcholine and oxotremorine, at concentrations ranging from 10(-9) to 10(-6) M inhibited the evoked release of [3H]-GABA in a concentration-dependent manner, while nicotine was without effect. Scopolamine and pirenzepine inhibited the effect of oxotremorine, while hexamethonium had no effect. The IC50 values for scopolamine and pirenzepine of the oxotremorine (3 X 10(-8) M)-induced inhibition were 1.02 X 10(-9) M and 9.78 X 10(-10) M, respectively. Noradrenaline, but not isoprenaline inhibited the evoked release of [3H]-GABA. Clonidine (10(-10)-10(-6) M) reduced the evoked release of [3H]-GABA in a concentration-dependent manner, but phenylephrine had no effect. The inhibitory effect of clonidine was antagonized by yohimbine but not by prazosin. These findings provide evidence for the localization of M1-muscarinic and alpha 2-adrenoceptors on GABAergic nerve terminals and their involvement in the presynaptic control of the release of GABA from the guinea-pig small intestine.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000294:innervation / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D010095:Oxotremorine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology*; D012601:Scopolamine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D011942:Receptors, Adrenergic, alpha; D011976:Receptors, Muscarinic; D010656:Phenylephrine; D005680:gamma-Aminobutyric Acid; D010095:Oxotremorine; D012601:Scopolamine; D007545:Isoproterenol; D003000:Clonidine; D011188:Potassium