Hu S B, Lightman S L, Tannahill L A
Neuroendocrinology Unit, Charing Cross and Westminster Medical School, Charing Cross Hospital, London, U.K.
Brain Res. 1992 Mar 6;574(1-2):266-70. doi: 10.1016/0006-8993(92)90826-u.
5-Hydroxytryptamine (5-HT) has been shown to activate the hypothalamo-pituitary-adrenal axis, possibly by a direct action on hypothalamic CRF synthesis and release. In order to study the mechanisms involved in this effect, foetal hypothalamic cells were cultured and corticotropin-releasing factor-41 (CRF) release was measured by radioimmunoassay. 5-HT induced CRF release in a dose-dependent manner. Further studies were performed with a specific protein kinase C inhibitor, H-7 (1-(5-isoquinolinesulfonyl)-2-methyl-piperazine) and a specific cyclic adenosine monophosphate-dependent protein kinase inhibitor, IP-20. Basal release of CRF-41 from the cultured hypothalamic cells was unaffected by IP-20 and was only diminished at a high (50 microM) concentration of H-7. 5-HT stimulated-CRF release, however, was blocked by both H-7 and IP-20. Dexamethasone and aldosterone both caused a dose-dependent inhibition of 5-HT induced CRF release. These results demonstrate that CRF can be released from hypothalamic neurons in response to 5-HT through a protein kinase C and protein kinase A dependent mechanism and that 5-HT stimulated CRF release can be inhibited by dexamethasone and aldosterone.
5-羟色胺（5-HT）已被证明可激活下丘脑-垂体-肾上腺轴，可能是通过直接作用于下丘脑促肾上腺皮质激素释放因子（CRF）的合成与释放。为了研究这一效应所涉及的机制，培养了胎儿下丘脑细胞，并通过放射免疫分析法测定促肾上腺皮质激素释放因子-41（CRF）的释放。5-HT以剂量依赖的方式诱导CRF释放。使用特异性蛋白激酶C抑制剂H-7（1-（5-异喹啉磺酰基）-2-甲基哌嗪）和特异性环磷酸腺苷依赖性蛋白激酶抑制剂IP-20进行了进一步研究。培养的下丘脑细胞中CRF-41的基础释放不受IP-20影响，仅在高浓度（50微摩尔）的H-7作用下有所减少。然而，5-HT刺激的CRF释放被H-7和IP-20均阻断。地塞米松和醛固酮均引起5-HT诱导的CRF释放的剂量依赖性抑制。这些结果表明，CRF可通过蛋白激酶C和蛋白激酶A依赖性机制从下丘脑神经元释放以响应5-HT，并且5-HT刺激的CRF释放可被地塞米松和醛固酮抑制。
