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 acetylcholine (ACh) from isolated ileal synaptosomal guinea-pig preparations was examined by means of high pressure liquid chromatography with electrochemical 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 concentration-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 guanethidine or desipramine to inhibit this effect of dopamine ruled out mediation by endogenous noradrenaline. 5. Idazoxan and yohimbine reversed this dopamine-induced inhibition at concentration sufficient to abolish the action of clonidine. Influx of (45)Ca stimulated by substance P or high potassium into synaptosomal preparations was attenuated in the presence of dopamine. This inhibition by dopamine was also reversed by idazoxan or yohimbine but not by dopamine receptor antagonists. Moreover, the dopamine-induced inhibitions of both the ACh release and the influx of (45)Ca disappeared in the samples treated with pertussis toxin at a dose sufficient to abolish the action of clonidine. 6. It is concluded that dopamine suppresses the influx of calcium ions into cholinergic nerve terminals via an activation of alpha2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding protein, resulting in the decrease of ACh release from ileal synaptosomes of guinea-pigs.
Chang
S S
SS
Department of Nursing Sciences, Chinese Junior College of Medical Technology, Taiwan, Republic of China.
Cheng
J T
JT
D000109:Acetylcholine / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004146:Dioxanes / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D005260:Female; D006168:Guinea Pigs; D019329:Idazoxan; D007082:Ileum / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D037342:Pertussis Toxin; D011188:Potassium / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D010566:Virulence Factors, Bordetella; D015016:Yohimbine; D013373:Substance P; D037342:Pertussis Toxin; D000109:Acetylcholine; D011188:Potassium; D002118:Calcium; D004298:Dopamine; D019329:Idazoxan