Gardiner I M, Li A, Patel N, Ball S, de Belleroche J
Department of Biochemistry, Charing Cross & Westminster Medical School, London.
Life Sci. 1992;51(8):PL77-81. doi: 10.1016/0024-3205(92)90235-h.
The enzyme ornithine decarboxylase (ODC) has been shown to be induced by a number of conditions such as cold-injury, kindling, ischaemia and excitotoxin injection. In previous studies we have characterised the cortical response to kainate injection into the nucleus basalis and shown a substantial increase in both ODC mRNA and enzyme activity which reaches a maximum at 8h. This response is completely prevented by treatment with MK-801, indicating the involvement of NMDA receptors in mediating this response. Whilst NMDA receptors are known to gate a cation channel leading to increased calcium entry, an additional effect on the release of arachidonic acid has been reported. The possibility that NMDA receptor mediated activation of phospholipase A2 and release of arachidonic acid might mediate this ODC response was investigated in this study by treatment with the phospholipase inhibitors quinacrine and dexamethasone. Treatment of animals with quinacrine (100 mg/kg) at the time of injection of kainate into the nucleus basalis caused a significant attenuation of the induction of ODC in cerebral cortex of 43%. No further attenuation was seen at higher doses. A similar reduction in ODC induction was seen after treatment with dexamethasone (1 mg/kg) but a greater effect could be obtained (65% attenuation) at higher doses. The possible involvement of arachidonic acid derivatives in mediating ODC induction was further investigated by treatment with the cyclo-oxygenase inhibitor indomethacin and the lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA). Indomethacin was able to significantly attenuate the induction of ODC (greater than 60%) whilst NDGA (30 mg/kg) was ineffective. These results indicate the possible role of arachidonic acid derivatives in the regulation of the expression of ODC in cerebral cortex after excitotoxin injection.
鸟氨酸脱羧酶（ODC）已被证明可由多种条件诱导，如冷损伤、点燃、缺血和注射兴奋性毒素。在先前的研究中，我们已对向基底核注射海藻酸后的皮质反应进行了表征，并显示ODC mRNA和酶活性均大幅增加，在8小时时达到最大值。用MK-801处理可完全阻止这种反应，表明NMDA受体参与介导此反应。虽然已知NMDA受体可开启阳离子通道导致钙内流增加，但也有报道称其对花生四烯酸释放有额外影响。本研究通过用磷脂酶抑制剂奎纳克林和地塞米松处理，探讨了NMDA受体介导的磷脂酶A2激活和花生四烯酸释放可能介导这种ODC反应的可能性。在向基底核注射海藻酸时用奎纳克林（100 mg/kg）处理动物，导致大脑皮质中ODC诱导的显著减弱，减弱了43%。在更高剂量下未见进一步减弱。用地塞米松（1 mg/kg）处理后也观察到ODC诱导有类似降低，但在更高剂量下可获得更大效果（减弱65%）。通过用环氧化酶抑制剂吲哚美辛和脂氧化酶抑制剂去甲二氢愈创木酸（NDGA）处理，进一步研究了花生四烯酸衍生物在介导ODC诱导中的可能作用。吲哚美辛能够显著减弱ODC的诱导（大于60%），而NDGA（30 mg/kg）无效。这些结果表明花生四烯酸衍生物在兴奋性毒素注射后大脑皮质中ODC表达的调节中可能起作用。
