GABA-ERGIC MECHANISMS INFLUENCING VASOPRESSIN RELEASE

这个项目的长期目标是了解 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的相互作用。 这项工作将揭示神经化学变化与 在AVP有助于整合生理的情况下， 维持血管张力，如限水和出血。 的 本提案的重点是检验伽马- 氨基丁酸（GABA）对释放的紧张性抑制 由生理刺激调节的血管加压素。 测量将 由：1）神经递质释放（GABA和去甲肾上腺素）在 下丘脑室旁核（控制AVP的区域 分泌）和2）血浆AVP水平和随后的血流动力学效应 的AVP。 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释放产生紧张性抑制作用。 休息的动物 其次，将进行实验以确定 如果GABA能活性在AVP分泌被刺激时降低， 渗透压挑战或压力感受器卸载通过降低动脉压。 在第三项研究中，将确定GABA的贡献， 压力感受性反射介导的AVP释放抑制。 在这些实验中，AVP 会受到渗透压刺激，然后压力感受器会 通过升高动脉压激活。 第四项研究将侧重于 GABA与兴奋性神经递质的潜在相互作用， 去甲肾上腺素 这表明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 去甲肾上腺素释放 这些研究将提供重要的新 深入了解控制生理活动的神经化学机制， AVP释放的调节。

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.