GABA-ERGIC MECHANISMS INFLUENCING VASOPRESSIN RELEASE

这个项目的长期目标是理解 精氨酸加压素(AVP)释放的生理刺激与 调节加压素分泌的神经递质之间的相互作用。 这项工作将揭示神经化学变化和 AVP参与的综合生理学研究 维持血管张力，如限水和出血。这个 本提议的重点是检验伽马- 氨基丁酸(GABA)对肾上腺素释放有紧张性抑制作用 受生理刺激调节的加压素。测量结果将 包括：1)脑内神经递质释放(GABA和去甲肾上腺素) 下丘脑室旁核(控制AVP的区域 分泌)和2)血浆AVP水平及随后的血流动力学效应 AVP的。使用这些方法，将解决四个具体目标。第一, 将确定GABA是否对AVP的释放起紧张性抑制作用 休息的动物。其次，将进行实验以确定 如果当AVP分泌被刺激时GABA能活性降低 通过降低动脉压进行渗透性挑战或压力感受器卸载。 在第三项研究中，将确定GABA对 压力感受性反射抑制AVP的释放。在这些实验中，AVP 会受到渗透挑战的刺激，那么压力感受器就会 通过升高动脉压来激活。第四项研究将集中于 GABA与兴奋性神经递质的潜在相互作用， 去甲肾上腺素。目前认为GABA通过以下途径发挥其抑制作用 直接阻断AVP分泌，间接干扰AVP分泌 去甲肾上腺素的释放。这些研究将提供重要的新的 对控制生理的神经化学机制的洞察 AVP释放的调控。

The long term goal of this program is to understand the relationship between physiological stimuli for arginine vasopressin (AVP) release and the interactions of neurotransmitters which regulate vasopressin secretion. This work will reveal relationships between neurochemical changes and integrative physiology in situations in which AVP contributes to the maintenance of vascular tone such as water restriction and hemorrhage. The focus of the present proposal is to test the hypothesis that gamma- aminobutyric acid (GABA) exerts a tonic inhibition on the release of vasopressin that is modulated by physiological stimuli. Measurements will be made of: 1) neurotransmitter release (GABA and norepinephrine) in the paraventricular nucleus of the hypothalamus (an area controlling AVP secretion) and 2) plasma AVP levels and the subsequent hemodynamic effects of AVP. Using these methods, four specific aims will be addressed. First, it will be determined if GABA exerts a tonic inhibition on AVP release in the resting animal. Secondly, experiments will be performed to determine if GABAergic activity decreases when AVP secretion is stimulated by an osmotic challenge or baroreceptor unloading by lowering arterial pressure. In the third study, the contribution of GABA will be determined to baroreflex-mediated inhibition of AVP release. In these experiments, AVP will be stimulated by an osmotic challenge, then the baroreceptors will be activated by raising arterial pressure. The fourth study will focus on the potential interaction of GABA with the excitatory neurotransmitter, norepinephrine. It is proposed that GABA exerts its inhibitory effect by acting directly to block AVP secretion and indirectly to interfere with norepinephrine release. These studies will provide significant new insights into the neurochemical mechanisms controlling the physiological regulation of AVP release.