Yamamoto Y, Tanaka T, Shibata S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Brain Res. 1994 Nov 28;665(1):151-4. doi: 10.1016/0006-8993(94)91166-5.
The effect of dopamine (DA) receptor agonists and antagonists on hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 presynaptic fiber spikes elicited by the stimulation of Schaffer collateral were investigated using hippocampal slices. Treatment with D1 dopamine receptor antagonist, SCH23390 produced a concentration-dependent attenuation of the ischemia-induced decrease of presynaptic potentials. The magnitude of recovery of the CA1 presynaptic potential in SCH233390-treated slices at 10 and 100 microM was 28 and 54%, respectively. Whereas, treatment with D1 dopamine receptor agonist, SKF38393 exacerbated the ischemia-induced decrease in the CA1 presynaptic potential. The decrease of CA1 presynaptic potential by ischemia was affected by neither D2 dopamine receptor agonist, bromocriptin and quinpirole nor D2 dopamine receptor antagonist, sulpiride. The neuroprotective effect of SCH23390 was completely blocked by cotreatment with SKF38393. The present results demonstrated that the blockade of D1 dopamine receptor function played a neuroprotective role in ischemic damage, suggesting a facilitatory role of D1 dopamine receptor-operated function in ischemia-induced neuronal deficits.
使用海马切片研究了多巴胺（DA）受体激动剂和拮抗剂对缺氧/低血糖（缺血）诱导的由刺激Schaffer侧支引起的CA1突触前纤维峰电位降低的影响。用D1多巴胺受体拮抗剂SCH23390处理可产生浓度依赖性地减轻缺血诱导的突触前电位降低。在10和100微摩尔浓度下，用SCH233390处理的切片中CA1突触前电位的恢复幅度分别为28%和54%。然而，用D1多巴胺受体激动剂SKF38393处理会加剧缺血诱导的CA1突触前电位降低。缺血导致的CA1突触前电位降低既不受D2多巴胺受体激动剂溴隐亭和喹吡罗的影响，也不受D2多巴胺受体拮抗剂舒必利的影响。与SKF38393共同处理可完全阻断SCH23390的神经保护作用。目前的结果表明，D1多巴胺受体功能的阻断在缺血损伤中起神经保护作用，提示D1多巴胺受体介导的功能在缺血诱导的神经元缺陷中起促进作用。
