Hansen Suzanne L, Fjalland Bjarne, Jackson Meyer B
Department of Pharmacology, The Danish University of Pharmaceutical Sciences, 2 Universitetsparken, 2100 Copenhagen, Denmark.
Pharmacol Toxicol. 2003 Aug;93(2):91-7. doi: 10.1034/j.1600-0773.2003.930206.x.
A number of neurosteroids bind to GABAA receptors and alter their responsiveness to neurotransmitters. Considerable effort has been devoted to understanding how this form of receptor modulation alters inhibitory synaptic function. Neurosteroid-sensitive GABAA receptors have also been demonstrated in many endocrine cells, but little is known about how neurosteroids modulate the release of hormones. Here, the action of allopregnanolone, a neurosteroid that enhances GABAA receptor-mediated responses, was investigated in posterior pituitary nerve terminals and intermediate pituitary endocrine cells. Patch clamp recordings showed that GABA-evoked currents were enhanced to similar degrees and with similar concentration dependences in both locations. An organ bath preparation of the neurointermediate lobe was used to investigate drug effects on secretion of vasopressin and alpha-melanocyte stimulating hormone. GABA increased the basal release of vasopressin and alpha-melanocyte stimulating hormone from the posterior and intermediate pituitary lobe, respectively, an effect that could be blocked by picrotoxinin. Vasopressin release evoked by electrical stimulation was also examined, and a small statistically significant inhibition by 5 microM GABA was observed. Allopregnanolone increased the basal release of vasopressin, and this effect was blocked by the GABAA receptor antagonist picrotoxinin. Allopregnanolone had no effect in conjunction with GABA. In contrast to the posterior lobe, allopregnanolone had no effect on release from the intermediate lobe. Thus, allopregnanolone in physiological relevant concentrations modulates GABAA receptors in both the posterior and intermediate lobes, but only affects hormone release in the posterior lobe.
许多神经甾体与GABAA受体结合并改变其对神经递质的反应性。人们已经付出了相当大的努力来理解这种受体调节形式如何改变抑制性突触功能。在许多内分泌细胞中也已证实存在对神经甾体敏感的GABAA受体，但关于神经甾体如何调节激素释放却知之甚少。在此，研究了别孕烯醇酮（一种增强GABAA受体介导反应的神经甾体）在垂体后叶神经末梢和垂体中间部内分泌细胞中的作用。膜片钳记录显示，在这两个部位，GABA诱发的电流均以相似程度增强且具有相似的浓度依赖性。采用神经中间叶的器官浴制备法来研究药物对血管加压素和α-黑素细胞刺激素分泌的影响。GABA分别增加了垂体后叶和中间叶血管加压素和α-黑素细胞刺激素的基础释放，该效应可被印防己毒素阻断。还检测了电刺激诱发的血管加压素释放，观察到5微摩尔GABA有轻微的统计学显著抑制作用。别孕烯醇酮增加了血管加压素的基础释放，且该效应被GABAA受体拮抗剂印防己毒素阻断。别孕烯醇酮与GABA联合使用时无作用。与垂体后叶不同，别孕烯醇酮对垂体中间叶的释放无影响。因此，生理相关浓度的别孕烯醇酮可调节垂体后叶和中间叶的GABAA受体，但仅影响垂体后叶的激素释放。
