Secretory phospholipase A2 activity in the normal and kainate injected rat brain, and inhibition by a peptide derived from python serum

Abstract

The present study aimed to elucidate sPLA2 activity in the normal and kainate-lesioned hippocampus using selective inhibitors of sPLA2. In normal rats the highest levels of sPLA2 were observed in the hippocampus, pons, and medulla, followed by the cerebral neocortex and caudate nucleus. After intracerebroventricular kainate injections an increase in total PLA2 activity was observed in the rat hippocampus. Using a selective sPLA2 inhibitor 12-epi-scalaradial, sPLA2 activity was found to be significantly increased by 2.5-fold on the side of the intracerebroventricular injection compared to the contralateral side. A peptide P-NT.II, derived from the amino acid sequence of "PLA2-inhibitory protein," discovered in the serum of the reticulated python, also showed potent sPLA2 inhibitory activity in homogenates from the kainate-injected hippocampus. These results show that there is a high level of sPLA2 activity in the normal hippocampus, pons, and medulla oblongata, and that the level increases further in the hippocampus after kainate-induced excitotoxic injury. The increased PLA2 activity was inhibited by P-NT.II, indicating a potential use of this peptide as a PLA2 inhibitory agent in the brain.