Marques de Souza Leandro, Franci Celso Rodrigues
Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirão Preto SP, Brazil.
Life Sci. 2008 Nov 7;83(19-20):686-92. doi: 10.1016/j.lfs.2008.09.007. Epub 2008 Sep 23.
The hypothalamus-pituitary-adrenal axis (HPA) participates in mediating the response to stressful stimuli. Within the HPA, neurons in the medial parvocellular region of paraventricular nucleus (PVN) of the hypothalamus integrate excitatory and inhibitory signals triggering secretion of corticotropin-releasing hormone (CRH), the main secretagogue of adrenocorticotropic hormone (ACTH). Stressful situations alter CRH secretion as well as other hormones, including prolactin and oxytocin. Most inputs to the PVN are of local origin, half of which are GABAergic neurons, and both GABA-A and GABA-B receptors are present in the PVN. The objective of the present study was to investigate the role of GABA-A and GABA-B receptors in the PVN's control of stress-induced corticosterone, oxytocin and prolactin secretion. Rats were microinjected with saline or different doses (0.5, 5 and 50 pmol) of GABA-A (bicuculine) or GABA-B (phaclofen) antagonists in the PVN. Ten minutes later, they were subjected to a stressor (ether inhalation) and blood samples were collected 30 min before and 10, 30, 60, 90 and 120 min after the stressful stimulus to measure hormone levels by radioimmunoassay. Our results indicate that GABA acts in the PVN to inhibit stress-induced corticosterone secretion via both its receptor subtypes, especially GABA-B. In contrast, GABA in the PVN stimulates oxytocin secretion through GABA-B receptors and does not alter prolactin secretion.
下丘脑-垂体-肾上腺轴(HPA)参与介导对应激刺激的反应。在HPA中,下丘脑室旁核(PVN)内侧小细胞区的神经元整合兴奋性和抑制性信号,触发促肾上腺皮质激素释放激素(CRH)的分泌,CRH是促肾上腺皮质激素(ACTH)的主要促分泌素。应激情况会改变CRH的分泌以及其他激素的分泌,包括催乳素和催产素。PVN的大多数输入来自局部,其中一半是γ-氨基丁酸能(GABAergic)神经元,并且PVN中同时存在GABA-A和GABA-B受体。本研究的目的是调查GABA-A和GABA-B受体在PVN对应激诱导的皮质酮、催产素和催乳素分泌的控制中的作用。将大鼠PVN内微量注射生理盐水或不同剂量(0.5、5和50皮摩尔)的GABA-A拮抗剂(荷包牡丹碱)或GABA-B拮抗剂(巴氯芬)。10分钟后,对它们施加应激源(乙醚吸入),并在应激刺激前30分钟以及刺激后10、30、60、90和120分钟采集血样,通过放射免疫测定法测量激素水平。我们的结果表明,GABA在PVN中通过其两种受体亚型发挥作用,抑制应激诱导的皮质酮分泌,尤其是GABA-B受体。相比之下,PVN中的GABA通过GABA-B受体刺激催产素分泌,并且不改变催乳素分泌。