Marcheselli V L, Bazan N G
Louisiana State University Medical Center, New Orleans 70112.
J Neurosci Res. 1994 Jan;37(1):54-61. doi: 10.1002/jnr.490370108.
Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), undetectable in resting neural tissue, accumulates in brain during seizures. A hetrazepine, BN-50730, is shown here to displace [3H]PAF-specific binding from microsomal, but not from synaptosomal membranes, indicating selectivity for a high affinity intracellular binding site. Rats pretreated with BN-50730 by intraperitoneal or intracerebroventricular injection exhibited an inhibition of the electroconvulsive shock (ECS)-induced expression of c-fos and zif-268 in hippocampus. A much more pronounced, dose-dependent inhibition of ECS-induced zif-268 mRNA in hippocampus by intracerebroventricular injection of BN-50730 was observed. It is concluded that, in the hippocampus, PAF is a mediator of the expression of zif-268 and, to a lesser extent, c-fos through an intracellular specific binding site. Thus, PAF may be a messenger in signal regulated zinc-finger transcription factors, and in other immediate-early genes involved in long-term synaptic plasticity changes.
血小板活化因子(PAF,1-O-烷基-2-乙酰基-sn-甘油-3-磷酸胆碱)在静息神经组织中无法检测到,但在癫痫发作时会在大脑中蓄积。本文显示一种庚氮卓类药物BN-50730能够取代微粒体膜而非突触体膜上的[3H]PAF特异性结合,表明其对高亲和力细胞内结合位点具有选择性。通过腹腔注射或脑室内注射BN-50730预处理的大鼠,海马体中电惊厥休克(ECS)诱导的c-fos和zif-268表达受到抑制。通过脑室内注射BN-50730,观察到对海马体中ECS诱导的zif-268 mRNA有更明显的剂量依赖性抑制作用。得出的结论是,在海马体中,PAF是zif-268表达的介质,在较小程度上也是c-fos表达的介质,通过细胞内特异性结合位点发挥作用。因此,PAF可能是信号调节锌指转录因子以及参与长期突触可塑性变化的其他早期即刻基因中的信使。