Ochi M, Koizumi S, Shibata S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Brain Res. 1994 Jan 7;633(1-2):91-6. doi: 10.1016/0006-8993(94)91526-1.
The excitatory amino acid, glutamate plays a crucial role in the pathogenesis of brain damage caused by anoxia and/or hypoglycemia. Although vasopressin (VP) also acts as an excitatory transmitter in the CNS, little is known about its effect on hypoxic and/or ischemic brain damage. In this study, we investigated the effect of arginine vasopressin (AVP) on hypoxia/hypoglycemia-induced impairment of dopamine release from striatal slices. Striatal slices were incubated in hypoxia-/hypoglycemia-inducing medium with or without AVP (0.01-1.0 microM) for 20 min. After 1-3 h of washout in normal medium, high K(+)-evoked dopamine release from the slices were examined. Hypoxia/hypoglycemia-induced decrease of striatal dopamine release was reversed by the removal of Ca2+ in the medium, but not by VP1- or VP2-receptor antagonist. In contrast, AVP potentiated the hypoxia/hypoglycemia-induced decrease of dopamine release in the striatum. This AVP-induced deterioration of the striatal response was antagonized by VP2 receptor antagonist, but not by VP1 receptor antagonist. The present results suggest that AVP may play a facilitatory role in hypoxia/hypoglycemia-induced dopamine release deficit mediated through the activation of VP2 receptor.
兴奋性氨基酸谷氨酸在缺氧和/或低血糖所致脑损伤的发病机制中起关键作用。虽然血管加压素（VP）在中枢神经系统中也作为一种兴奋性递质发挥作用，但其对缺氧和/或缺血性脑损伤的影响却知之甚少。在本研究中，我们调查了精氨酸血管加压素（AVP）对缺氧/低血糖诱导的纹状体切片多巴胺释放受损的影响。将纹状体切片在含有或不含有AVP（0.01 - 1.0微摩尔）的缺氧/低血糖诱导培养基中孵育20分钟。在正常培养基中洗脱1 - 3小时后，检测切片中高钾诱发的多巴胺释放。缺氧/低血糖诱导的纹状体多巴胺释放减少可通过去除培养基中的Ca2 +而逆转，但VP1或VP2受体拮抗剂不能逆转。相反，AVP增强了缺氧/低血糖诱导的纹状体多巴胺释放减少。VP2受体拮抗剂可拮抗AVP诱导的纹状体反应恶化，但VP1受体拮抗剂不能。目前的结果表明，AVP可能通过激活VP2受体在缺氧/低血糖诱导的多巴胺释放缺陷中起促进作用。
