Blasquez C, Jégou S, Delarue C, Delbende C, Bunel D T, Braquet P, Vaudry H
URA CNRS 650, Unité Affiliée à l'INSERM, Université de Rouen, Mont-Saint-Aignan, France.
Eur J Pharmacol. 1990 Feb 27;177(3):145-53. doi: 10.1016/0014-2999(90)90264-7.
To examine the effect of platelet-activating factor (PAF-acether) on pro-opiomelanocortin (POMC)-related peptides and on the hypothalamo-pituitary-adrenal axis, we administered PAF-acether and BN 52021, a selective PAF-acether antagonist, to freely moving rats. Minipumps loaded with either PAF-acether (30 micrograms/kg) or the vehicle alone were connected to the jugular vein for 7 days and positioned under the back skin of rats. A group of animals treated with PAF-acether also received 15 mg/kg of BN 52021 orally twice a day. In vivo treatment with PAF-acether alone or in association with BN 52021 did not affect the hypothalamic concentrations of corticotropin-releasing factor (CRF), alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin. Using a perifusion system for rat hypothalamic slices, we did not observe any effect of PAF-acether on spontaneous or potassium-induced release of alpha-MSH in vitro. In addition, treatment of rats with PAF-acether alone or in association with BN 52021 did not modify the alpha-MSH or beta-endorphin concentration in the neurointermediate lobe of the pituitary. In contrast, in vivo administration of PAF-acether caused a significant reduction of ACTH concentration in the anterior lobe of the pituitary and a marked decrease in the corticosterone level in plasma and adrenal glands. The inhibitory effect of PAF-acether was reversed by concomitant administration of BN 52021. The ineffectiveness of PAF-acether to modulate in vitro ACTH release from perifused anterior pituitary fragments ruled out a direct effect of PAF-acether on corticotrophs. These findings support the view that PAF-acether exerts a specific inhibitory effect on the hypothalamo-pituitary-adrenal axis.
为研究血小板活化因子（PAF - 乙醚）对阿片 - 促黑素 - 皮质素原（POMC）相关肽以及下丘脑 - 垂体 - 肾上腺轴的影响，我们将PAF - 乙醚和选择性PAF - 乙醚拮抗剂BN 52021给予自由活动的大鼠。将装有PAF - 乙醚（30微克/千克）或仅含赋形剂的微型泵连接到大鼠颈静脉7天，并置于大鼠背部皮肤下方。一组接受PAF - 乙醚治疗的动物还每天口服两次15毫克/千克的BN 52021。单独使用PAF - 乙醚或与BN 52021联合进行体内治疗，均未影响下丘脑促肾上腺皮质激素释放因子（CRF）、α - 黑素细胞刺激素（α - MSH）和β - 内啡肽的浓度。使用大鼠下丘脑切片的灌流系统，我们未观察到PAF - 乙醚对体外α - MSH的自发释放或钾诱导释放有任何影响。此外，单独使用PAF - 乙醚或与BN 52021联合治疗大鼠，均未改变垂体神经中间叶中α - MSH或β - 内啡肽的浓度。相比之下，体内给予PAF - 乙醚导致垂体前叶促肾上腺皮质激素（ACTH）浓度显著降低，血浆和肾上腺中皮质酮水平明显下降。同时给予BN 52021可逆转PAF - 乙醚的抑制作用。PAF - 乙醚对灌流的垂体前叶片段体外ACTH释放无调节作用，排除了PAF - 乙醚对促肾上腺皮质激素细胞的直接作用。这些发现支持了PAF - 乙醚对下丘脑 - 垂体 - 肾上腺轴具有特异性抑制作用的观点。
