DOPAMINE-INDUCED INHIBITION OF ENDOGENOUS ACETYLCHOLINE-RELEASE FROM THE ISOLATED ILEAL SYNAPTOSOMAL PREPARATIONS OF GUINEA-PIG MEDIATED VIA ALPHA-ADRENOCEPTORS

1 The effect of exogenous dopamine on the release of endogenous acetyl choline (ACh) from isolated ileal synaptosomal guinea-pig preparations was examined by means of high pressure liquid chromatography with ele ctrochemical detection. 2 Release of ACh was induced by substance P or by depolarization with high potassium (50 mM) in a medium containing atropine, propranolol and naloxone. 3 Dopamine produced a concentratio n-dependent inhibition of the evoked ACh release induced by substance P or in samples depolarized by high potassium. This action of dopamine was not reversed by the dopamine receptor antagonists either for the DA2 subtype, domperidone, or for the DA1 subtype, SCH23390. Fenoldopam , the agonist of dopamine DA1 receptors, or quinpirole, the agonist of dopamine DA2 receptors, reduced the evoked ACh release, although only in high, non-dopamine-specific concentrations. 4 Failure of guanethid ine or desipramine to inhibit this effect of dopamine ruled out mediat ion by endogenous noradrenaline. 5 Idazoxan and yohimbine reversed thi s dopamine-induced inhibition at concentrations sufficient to abolish the action of clonidine. Influx of Ca-45 stimulated by substance P or high potassium into synaptosomal preparations was attenuated in the pr esence of dopamine. This inhibition by dopamine was also reversed by i dazoxan or yohimbine but not by dopamine receptor antagonists. Moreove r, the dopamine-induced inhibitions of both the ACh release and the in flux of Ca-45 disappeared in the samples treated with pertussis toxin at a dose sufficient to abolish the action of clonidine. 6 It is concl uded that dopamine suppresses the influx of calcium ions into choliner gic nerve terminals via an activation of alpha(2)-adrenoceptors couple d with a pertussis toxin-sensitive GTP-binding protein, resulting in t he decrease of ACh release from ileal synaptosomes of guinea-pigs.