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5-羟色胺1A受体激动剂8-羟基二丙基氨基四氢吡啶(8OHDPAT)对大鼠促肾上腺皮质激素(ACTH)和催乳素(PRL)分泌的不同作用位点

Differential sites of action of 8OHDPAT, a 5HT1A agonist, on ACTH and PRL secretion in the rat.

作者信息

Bluet Pajot M T, Mounier F, di Sciullo A, Schmidt B, Kordon C

机构信息

Unité de Recherches Dynamique des Systèmes Neuroendocriniens, U. 159 INSERM, Paris, France.

出版信息

Neuroendocrinology. 1995 Feb;61(2):159-66. doi: 10.1159/000126836.

DOI:10.1159/000126836
PMID:7753334
Abstract

We recently obtained evidence that activation of the 5HT1A subtype receptor enhances both plasma ACTH and prolactin (PRL) concentrations in rats. In order to explore the possible neuroanatomical structures involved in this interaction, we examined ACTH and PRL responses to intracerebral infusions of the 5HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8OHDPAT). In addition we also tested in vitro effects of 8OHDPAT added to the perifusion medium of pituitary cells or of hypothalamic slices on hormone or neurotransmitter release, respectively. The ACTH response to 8OHDPAT (0.1 mg/kg) was decreased after depletion of endogenous 5HT stores by p-chlorophenylalanine (PCPA) treatment. In contrast, the PRL response was markedly increased under that condition. Infusion of 8OHDPAT (1 microgram/microliter/15 min) into the dorsal raphe nucleus induced a slow elevation of ACTH release but was ineffective on PRL secretion while infusion of 8OHDPAT into the PVN induced a moderate elevation of both ACTH and PRL. After bilateral destruction of the PVN, PRL response to 8OHDPAT (0.1 and 0.25 mg/kg) was markedly potentiated. In contrast, PVN-lesioned animals showed a blunted ACTH response to 8OHdPAT. Basal or CRF-stimulated ACTH secretion rates from perifused dispersed adenohypophyseal cells were not affected by 8OHDPAT but the 5HT1A agonist induced a very slight and transient inhibition of PRL release. 8OHDPAT antagonized, in a dose-dependent manner, the K(+)-induced release of 3H-DA previously taken up in neurons of mediobasal hypothalamic slices. This data suggests that major sites of 5HT1A interaction in PRL and ACTH regulation are located within the CNS and not in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

我们最近获得的证据表明,5HT1A 亚型受体的激活会提高大鼠血浆促肾上腺皮质激素(ACTH)和催乳素(PRL)的浓度。为了探究参与这种相互作用的可能神经解剖结构,我们检测了对脑内注入 5HT1A 受体激动剂 8-羟基-2-(二正丙基氨基)四氢萘(8OHDPAT)时 ACTH 和 PRL 的反应。此外,我们还分别测试了添加到垂体细胞或下丘脑切片灌流培养基中的 8OHDPAT 对激素或神经递质释放的体外作用。用对氯苯丙氨酸(PCPA)处理耗尽内源性 5-羟色胺(5HT)储备后,对 8OHDPAT(0.1mg/kg)的 ACTH 反应降低。相反,在该条件下 PRL 反应显著增加。向中缝背核注入 8OHDPAT(1 微克/微升/15 分钟)会导致 ACTH 释放缓慢升高,但对 PRL 分泌无效,而向室旁核(PVN)注入 8OHDPAT 会使 ACTH 和 PRL 都适度升高。双侧损毁 PVN 后,对 8OHDPAT(0.1 和 0.25mg/kg)的 PRL 反应明显增强。相反,PVN 损伤的动物对 8OHdPAT 的 ACTH 反应减弱。来自灌流分散腺垂体细胞的基础或促肾上腺皮质激素释放因子(CRF)刺激的 ACTH 分泌率不受 8OHDPAT 影响,但 5HT1A 激动剂对 PRL 释放有非常轻微和短暂的抑制作用。8OHDPAT 以剂量依赖方式拮抗先前摄取到下丘脑基底部切片神经元中的 K(+)诱导的 3H-多巴胺(3H-DA)释放。这些数据表明,5HT1A 在 PRL 和 ACTH 调节中相互作用的主要部位位于中枢神经系统(CNS)内,而非垂体。(摘要截短于 250 字)

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