Tanaka T, Shishido Y, Shibata S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Brain Res. 1994 May 2;644(2):343-6. doi: 10.1016/0006-8993(94)91701-9.
We investigated the effects of vasopressin-related neuropeptides on the hypoxia/hypoglycemia (ischemia)-induced decrease of the CA1 presynaptic potential elicited by stimulation of Schaffer collaterals in rat hippocampal slices. Treatment with arginine-vasopressin (AVP) potentiated the ischemic decrease of the CA1 presynaptic potential. In contrast, a V1 receptor antagonist produced a dose-dependent neuroprotective effect, whereas a V2 receptor antagonist had no effect. The AVP-induced decrease of the CA1 presynaptic potential was completely blocked by simultaneous application of the V1 receptor antagonist. Because AVP4-9 is regarded as the major proteolytic product of AVP in the rat brain, we examined its effect on the ischemic decrease of the CA1 presynaptic potential. Treatment with AVP4-9 produced a more marked reduction of the potential than treatment with AVP itself. The present study demonstrates that stimulation of the V1 receptor has a detrimental effect on the development of ischemic damage whereas V1 receptor blockade has a neuroprotective effect, suggesting that AVP may potentiate ischemic neuronal deficits via V1 receptor stimulation.
我们研究了血管加压素相关神经肽对缺氧/低血糖（缺血）诱导的大鼠海马切片中刺激Schaffer侧支所引发的CA1突触前电位降低的影响。用精氨酸血管加压素（AVP）处理可增强CA1突触前电位的缺血性降低。相反，V1受体拮抗剂产生剂量依赖性神经保护作用，而V2受体拮抗剂则无作用。同时应用V1受体拮抗剂可完全阻断AVP诱导的CA1突触前电位降低。由于AVP4-9被认为是大鼠脑中AVP的主要蛋白水解产物，我们研究了其对CA1突触前电位缺血性降低的影响。用AVP4-9处理比用AVP本身处理能更显著地降低该电位。本研究表明，刺激V1受体对缺血性损伤的发展有有害作用，而阻断V1受体则有神经保护作用，提示AVP可能通过刺激V1受体增强缺血性神经元缺陷。
