Melittin enhances amino acid and free fatty acid release from the in vivo cerebral cortex

The effects of the phospholipase activator melittin on amino acid and free fatty acid release from the rat cerebral cortex were monitored and compared with those of a secretory PLA 2, using a cortical cup technique with topical application of these agents in artificial cerebrospinal fluid. Melittin (10 μg/ml; 3.5 μM) elicited a rapid increase in the levels of superfusate amino acids; aspartate, glutamate, GABA, glycine, taurine, glutamine, phosphoethanolamine, alanine, serine and the free fatty acids arachidonic, linoleic, palmitic and oleic acid. PLA 2 (25 μg/ml) also enhanced amino acid efflux but its effects were significantly slower to develop than those of melittin. The results confirm previous indications of an ability of phospholipases to augment extracellular levels of several amino acids, including the excitotoxins glutamate and aspartate, and further implicate phospholipase activation as a significant contributor to cerebral ischemic injury. Melittin has the potential to be a useful tool with which to evaluate the role of phospholipases in ischemia injury.