Tyagi M G, Handa R K, Stephen P M, Bapna J S
Department of Neuropsychopharmacology, Institute of Human Behavior and Allied Sciences, Delhi,
Biol Signals Recept. 1998 Nov-Dec;7(6):328-36. doi: 10.1159/000014556.
The neurohypophyseal hormone vasopressin (AVP) is widely distributed throughout the central nervous system. It acts as an excitatory transmitter in the CNS and plays an important physiological role in water and electrolyte homeostasis. However, water deprivation has been shown to induce changes in the levels of monoamines, but there is little knowledge about the influence of AVP on monoamine levels after water deprivation. In this study, we investigated the effect of AVP and its receptor antagonists on alterations in dopamine (DA) release and cyclic adenosine 3',5' monophosphate (cAMP) efflux from rat brain slices following water deprivation. Striatal brain slices (500 microm thick) were incubated in a medium with or without AVP (0. 1-1.0 microM) for 30 min. After 2 h of washout in normal medium, high KCl (40 mM)-evoked DA release and cAMP efflux from the rat brain slices were examined. In the brain slices of euhydrated animals, treatment with AVP slightly altered DA release and cAMP efflux from the brain. This increase in DA release and cAMP efflux was not significantly affected by the addition of a calcium/calmodulin-dependent protein phosphatase, calcineurin (20 microM), to the incubation medium or either by a V1 or V2 AVP receptor antagonist. In contrast, AVP significantly increased the DA release and enhanced the cAMP efflux from the brain slices of water-deprived animals. The AVP-induced increase of brain response in the water-deprived animals was significantly attenuated by a V2 receptor antagonist, partially by calcineurin, but not by a V1 receptor antagonist. The present results suggest that AVP may play a role in water-deprivation-induced DA release and cAMP efflux, which is possibly mediated through the activation of the V2 receptor. The V2 receptor action is attenuated by calcium/calmodulin-dependent dephosphorlyation of some cellular proteins critical for signal transduction.
神经垂体激素血管加压素（AVP）广泛分布于整个中枢神经系统。它在中枢神经系统中作为一种兴奋性递质，在水和电解质稳态中发挥重要的生理作用。然而，已表明缺水会导致单胺水平发生变化，但关于缺水后AVP对单胺水平的影响却知之甚少。在本研究中，我们研究了AVP及其受体拮抗剂对缺水后大鼠脑片多巴胺（DA）释放和环磷酸腺苷（cAMP）流出变化的影响。将纹状体脑片（500微米厚）在含有或不含有AVP（0.1 - 1.0微摩尔）的培养基中孵育30分钟。在正常培养基中冲洗2小时后，检测高钾（40毫摩尔）诱发的大鼠脑片DA释放和cAMP流出。在水分充足动物的脑片中，用AVP处理对脑片的DA释放和cAMP流出有轻微改变。向孵育培养基中添加钙/钙调蛋白依赖性蛋白磷酸酶钙调神经磷酸酶（20微摩尔），或添加V1或V2 AVP受体拮抗剂，均未显著影响DA释放和cAMP流出的这种增加。相比之下，AVP显著增加了缺水动物脑片的DA释放并增强了cAMP流出。AVP诱导的缺水动物脑反应增加被V2受体拮抗剂显著减弱，部分被钙调神经磷酸酶减弱，但未被V1受体拮抗剂减弱。目前的结果表明，AVP可能在缺水诱导的DA释放和cAMP流出中起作用，这可能是通过V2受体的激活介导的。V2受体的作用通过对信号转导至关重要的一些细胞蛋白的钙/钙调蛋白依赖性去磷酸化而减弱。
