Pan L, Gilbert F
Centre de Recherche, Hôpital Maisonneuve-Rosemont, Montréal, Canada.
Neuroendocrinology. 1992 Dec;56(6):797-802. doi: 10.1159/000126332.
Previous studies have shown that activation of the 5-HT1A receptor subtype enhances rat plasma ACTH concentration. Such receptors have been suggested to be located on CRH neuronal cell bodies in the paraventricular nuclei of the hypothalamus (PVN). In this report, microinjection of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT), a selective 5-HT1A agonist, into the PVN increased rat plasma ACTH concentration in a dose-related manner. Similar responses were observed when two other 5-HT1A agonists, busipirone and gepirone, were used. (+/-)-Pindolol, known to have 5-HT1A antagonist properties, blocked the effect induced by an optimal dose of 8-OH-DPAT after injection into the PVN. This same dose of 8-OH-DPAT also induced a decrease of hypothalamic CRH concentration, which was completely antagonized as well by pretreatment injection of (+/-)-pindolol into the PVN. A significant inverse correlation was found between hypothalamic CRH and plasma ACTH levels. These results confirm that elevation of the plasma ACTH concentration induced by 5-HT1A receptor subtype activation is mediated by the release of CRH from the paraventricular nuclei of the hypothalamus in rats, but do not exclude other mechanisms.
以往的研究表明，5-HT1A受体亚型的激活可提高大鼠血浆促肾上腺皮质激素（ACTH）浓度。有人认为这类受体位于下丘脑室旁核（PVN）中促肾上腺皮质激素释放激素（CRH）神经元的细胞体上。在本报告中，向PVN微量注射选择性5-HT1A激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT），可使大鼠血浆ACTH浓度呈剂量依赖性增加。使用另外两种5-HT1A激动剂丁螺环酮和吉哌隆时也观察到类似反应。已知具有5-HT1A拮抗剂特性的（±）-吲哚洛尔，在注射到PVN后可阻断最佳剂量的8-OH-DPAT所诱导的效应。同样剂量的8-OH-DPAT还可导致下丘脑CRH浓度降低，而向PVN预先注射（±）-吲哚洛尔也可完全拮抗这一效应。下丘脑CRH与血浆ACTH水平之间存在显著的负相关。这些结果证实，5-HT1A受体亚型激活所诱导的血浆ACTH浓度升高是由大鼠下丘脑室旁核释放CRH介导的，但不排除其他机制。
