Group IIA secretory phospholipase A 2 stimulates exocytosis and neurotransmitter release in pheochromocytoma-12 cells and cultured rat hippocampal neurons

Abstract

Recent evidence shows that secretory phospholipase A 2 (sPLA 2) may play a role in membrane fusion and fission, and may thus affect neurotransmission. The present study therefore aimed to elucidate the effects of sPLA 2 on vesicle exocytosis. External application of group IIA sPLA 2 (purified crotoxin subunit B or purified human synovial sPLA 2) caused an immediate increase in exocytosis and neurotransmitter release in pheochromocytoma-12 (PC12) cells, detected by carbon fiber electrodes placed near the cells, or by changes in membrane capacitance of the cells. EGTA and a specific inhibitor of sPLA 2 activity, 12-epi-scalaradial, abolished the increase in neurotransmitter release, indicating that the effect of sPLA 2 was dependent on calcium and sPLA 2 enzymatic activity. A similar increase in neurotransmitter release was also observed in hippocampal neurons after external application of sPLA 2, as detected by changes in membrane capacitance of the neurons. In contrast to external application, internal application of sPLA 2 to PC12 cells and neurons produced blockade of neurotransmitter release. Our recent studies showed high levels of sPLA 2 activity in the normal rat hippocampus, medulla oblongata and cerebral neocortex. The sPLA 2 activity in the hippocampus was significantly increased, after kainate-induced neuronal injury. The observed effects of sPLA 2 on neurotransmitter release in this study may therefore have a physiological, as well as a pathological role.