Ferchmin P A, DiScenna P, Borroni A M, Morales Velez M, Rivera E M, Teyler T J
Department of Biochemistry, School of Medicine, Universidad Central del Caribe, Bayamón, PR 00960.
Brain Res. 1993 Jan 22;601(1-2):95-102. doi: 10.1016/0006-8993(93)91699-s.
We tested the effect of DL-alpha-(difluoromethyl)ornithine (DFMO), a specific inhibitor of ornithine decarboxylase (ODC), on recordings in area CA1 of rat hippocampal slices. In the concentration range in which it is used as an ODC inhibitor, DFMO increased neuronal excitability and blocked paired-pulse inhibition. The effect of DFMO was reversed by perfusing the slice with normal bathing solution. These effects were not attenuated by the simultaneous addition of putrescine; thus the activity of DFMO was not related to a decrease in putrescine caused by the inhibition of ODC. Mediation by the N-methyl-D-aspartate (NMDA) receptor was ruled out because DL-2-amino-5-phosphonovalerate (APV), an NMDA antagonist, did not block the effect of DFMO. Intracellular and extracellular recordings of pharmacologically isolated IPSPs supported the notion that DFMO depressed GABAergic transmission. DFMO has frequently been used as a tool to study the role of the ODC-polyamine system in neural preparations. This report suggests that the results from such studies must be interpreted with caution. In addition, our findings raise questions about the proposed use of DFMO as a neuroprotective agent against excitotoxicity.
我们测试了鸟氨酸脱羧酶（ODC）的特异性抑制剂DL-α-（二氟甲基）鸟氨酸（DFMO）对大鼠海马切片CA1区记录的影响。在用作ODC抑制剂的浓度范围内，DFMO增加了神经元兴奋性并阻断了双脉冲抑制。用正常的浴液灌注切片可逆转DFMO的作用。同时添加腐胺并不会减弱这些作用；因此，DFMO的活性与ODC抑制导致的腐胺减少无关。由于NMDA拮抗剂DL-2-氨基-5-磷酸戊酸（APV）不能阻断DFMO的作用，因此排除了N-甲基-D-天冬氨酸（NMDA）受体的介导作用。药理学分离的抑制性突触后电位（IPSP）的细胞内和细胞外记录支持了DFMO抑制GABA能传递的观点。DFMO经常被用作研究ODC-多胺系统在神经制剂中的作用的工具。本报告表明，此类研究结果必须谨慎解读。此外，我们的研究结果对将DFMO用作抗兴奋性毒性神经保护剂的提议提出了质疑。
