Di Sciullo A, Bluet-Pajot M T, Mounier F, Oliver C, Schmidt B, Kordon C
U.159 INSERM, Paris, France.
Endocrinology. 1990 Aug;127(2):567-72. doi: 10.1210/endo-127-2-567.
Although the role of serotonin (5HT) in the regulation of anterior pituitary hormone secretion is well documented, the involvement of specific 5HT receptor subtypes in this action is not yet fully elucidated. In the present work we attempted to determine the neuroendocrine role of the 5HT1A receptor subtype. This was chosen mainly because highly selective pharmacological tools are available for that subtype. 8-Hydroxy-2-(di-n-propylamino)tetralin (8OHDPAT) and ipsapirone were injected iv in conscious, freely moving male rats cannulated in the jugular vein. For the sake of comparison, a 5HT receptor agonist with preference for the 5HT1B and 5HT1C receptor subtypes 1-(m-trifluoromethyl-phenyl)piperazine (TFMPP) was also administered. Plasma PRL, ACTH, and beta-endorphin levels increased in a dose-dependent manner after 8-OHDPAT (0.01-1 mg/kg) or ipsapirone (0.5-7.5 mg/kg) injection. Maximal effects were obtained between 7-15 min. Only the highest dose of 1-(m-trifluoromethyl-phenyl)piperazine (5 mg/kg) resulted in the same response. In contrast, none of the drugs used affected plasma GH, TSH, or LH levels at any dose tested. The results indicate that 5HT1A receptors are involved in the regulation of PRL as well as ACTH and beta-endorphin secretion. 8OHDPAT was almost 40 times more potent than ipsapirone. The maximal effects of the two drugs on PRL release were comparable. In contrast, ipsapirone behaved as a partial agonist only on ACTH and beta-endorphin secretion, thus suggesting that different neuronal targets are involved in the stimulation of the three hormones by 5HT.
尽管血清素（5HT）在调节垂体前叶激素分泌中的作用已有充分记载，但特定5HT受体亚型在这一作用中的参与情况尚未完全阐明。在本研究中，我们试图确定5HT1A受体亚型的神经内分泌作用。选择该亚型主要是因为有针对该亚型的高选择性药理学工具。将8-羟基-2-（二正丙基氨基）四氢萘（8OHDPAT）和 ipsapirone静脉注射到颈静脉插管的清醒、自由活动的雄性大鼠体内。为作比较，还给予了对5HT1B和5HT1C受体亚型有偏好的5HT受体激动剂1-（间三氟甲基苯基）哌嗪（TFMPP）。注射8-OHDPAT（0.01 - 1mg/kg）或ipsapirone（0.5 - 7.5mg/kg）后，血浆催乳素（PRL）、促肾上腺皮质激素（ACTH）和β-内啡肽水平呈剂量依赖性升高。在7 - 15分钟之间达到最大效应。只有最高剂量的1-（间三氟甲基苯基）哌嗪（5mg/kg）产生相同反应。相比之下，在所测试的任何剂量下，所用药物均未影响血浆生长激素（GH）、促甲状腺激素（TSH）或促黄体生成素（LH）水平。结果表明，5HT1A受体参与PRL以及ACTH和β-内啡肽分泌的调节。8OHDPAT的效力几乎比ipsapirone强40倍。两种药物对PRL释放的最大效应相当。相比之下，ipsapirone仅对ACTH和β-内啡肽分泌表现为部分激动剂，因此表明5HT对这三种激素的刺激涉及不同的神经元靶点。
