Sloley B D, Trudeau V L, Dulka J G, Peter R E
Department of Zoology, University of Alberta, Edmonton, Canada.
Can J Physiol Pharmacol. 1991 Jun;69(6):776-81. doi: 10.1139/y91-116.
The effects of the dopamine type-2 receptor (D-2) antagonist domperidone on pituitary and brain amine concentrations and serum gonadotropin levels in the goldfish were investigated. Domperidone caused a long-lasting, dose-dependent depletion of dopamine in the goldfish pituitary. Pituitary concentrations of 5-hydroxytryptamine (5HT) were unaffected by domperidone treatment. Concentrations of noradenaline, dopamine, and 5HT in the hypothalamus and telencephalon were also unaffected by domperidone treatment. In contrast to the goldfish, dopamine levels in both mouse pituitary and hypothalamus were unaffected by domperidone treatment. The depletion of dopamine was observed in both sexually regressed and recrudescent, male and female fish, but elevation of serum gonadotropin levels in response to domperidone treatment occurred only in sexually recrudescent fish. Treatment of sexually recrudescent fish with the D-2 antagonists pimozide, (-)-sulpiride and eticlopride and the dopamine type-1 (D-1) antagonists SKF 83566 and SCH 23390 failed to elicit a depletion of pituitary dopamine or elevation of serum gonadotropin. Treatment of sexually recrudescent fish with domperidone, alpha-methyl-p-tyrosine or carbidopa elicited comparable depletions of pituitary dopamine and elevations of serum gonadotropin. The results suggest that in addition to D-2 receptor antagonist activity, domperidone has some other neuropharmacological action on dopaminergic neurones in the goldfish pituitary.
研究了多巴胺2型受体(D-2)拮抗剂多潘立酮对金鱼垂体和脑内胺类浓度以及血清促性腺激素水平的影响。多潘立酮导致金鱼垂体中多巴胺出现持久的、剂量依赖性的耗竭。垂体中5-羟色胺(5HT)的浓度不受多潘立酮处理的影响。下丘脑和端脑中去甲肾上腺素、多巴胺和5HT的浓度也不受多潘立酮处理的影响。与金鱼不同,多潘立酮处理对小鼠垂体和下丘脑的多巴胺水平均无影响。在性消退和性复萌的雄鱼和雌鱼中均观察到多巴胺的耗竭,但多潘立酮处理引起的血清促性腺激素水平升高仅发生在性复萌的鱼中。用D-2拮抗剂匹莫齐特、(-)-舒必利和依替必利以及多巴胺1型(D-1)拮抗剂SKF 83566和SCH 23390处理性复萌的鱼,未能引起垂体多巴胺的耗竭或血清促性腺激素的升高。用多潘立酮、α-甲基-对-酪氨酸或卡比多巴处理性复萌的鱼,引起了相当的垂体多巴胺耗竭和血清促性腺激素升高。结果表明,除了D-2受体拮抗剂活性外,多潘立酮对金鱼垂体中的多巴胺能神经元还有一些其他的神经药理学作用。