Kagami Y, Shigenobu S, Watanabe S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Eur J Pharmacol. 1992 Nov 24;224(1):51-6. doi: 10.1016/0014-2999(92)94817-f.
The effect of 5-HT3 receptor agonists and antagonists on the hypoxia/hypoglycemia (ischemia)-induced decrease in CA1 field potential elicited by stimulation of Schaffer collaterals was investigated using rat hippocampal slices. Treatment with the 5-HT3 receptor agonist, 2-methyl-5-HT (1-10 microM), exacerbated the ischemia-induced decreased in CA1 field potential, whereas treatment with the 5-HT3 receptor antagonist, Y-25130 (0.1-100 microM), or the 5-HT2 receptor antagonist, ketanserin (10, 100 microM), produced dose-dependent neuroprotection against the ischemia-induced decrease. However, in normal non-ischemic solution these treatments did not significantly change the CA1 field potential. The protective action of Y-25130 was blocked by co-treatment with 2-methyl-5-HT. The magnitude of protection in the Y-25130-treated group (EC50, 1.8 microM) was about 20 times greater than that in the ketanserin-treated group (EC50, 33 microM). The present study demonstrated that stimulation of 5-HT3 receptors plays a detrimental role in the development of ischemic damage, whereas blockade of the 5-HT3 receptor plays a neuroprotective role in ischemic damage, suggesting a facilitatory role of 5-HT neurons in ischemia-induced neuronal deficits.
使用大鼠海马切片，研究了5-羟色胺3（5-HT3）受体激动剂和拮抗剂对缺氧/低血糖（缺血）诱导的、由刺激海马Schaffer侧支所引发的CA1区场电位降低的影响。用5-HT3受体激动剂2-甲基-5-HT（1-10微摩尔）处理，会加剧缺血诱导的CA1区场电位降低，而用5-HT3受体拮抗剂Y-25130（0.1-100微摩尔）或5-HT2受体拮抗剂酮色林（10、100微摩尔）处理，则产生剂量依赖性的神经保护作用，对抗缺血诱导的降低。然而，在正常的非缺血溶液中，这些处理并未显著改变CA1区场电位。Y-25130的保护作用会被与2-甲基-5-HT共同处理所阻断。Y-25130处理组（半数有效浓度，1.8微摩尔）的保护程度比酮色林处理组（半数有效浓度，33微摩尔）大20倍左右。本研究表明，刺激5-HT3受体在缺血性损伤的发展中起有害作用，而阻断5-HT3受体在缺血性损伤中起神经保护作用，提示5-羟色胺神经元在缺血诱导的神经元功能缺损中起促进作用。
