Effect of N-acetyl-aspartyl-glutamate (Naaga) on in-vitro leukotriene synthesis by macrophage cell line P388D1

The magnesium salt of N acetyl-aspartyl glutamic acid (Naaga), used in ophthalmic allergies, is a synthetic dipeptide analogue of a natural peptide found in mammalian brains. It has been shown in vitro that Naaga inhibits complement activation, mast-cell degranulation and leukotriene anaphylactic release. In order to verify Naaga's action on leukotriene production, we used the macrophage cell line P388D1 activated by calcium ionophore A23187. Leukotriene determination was performed by high-performance liquid chromatography. It was found that Naaga inhibits 15 to 80% macrophage eicosanoid secretion (10(-9) M to 10(-2) M), acting mainly on LTC4-D4-E4 synthesis. Naaga was as potent as the leukotriene inhibitor nordihydroguaiaretic acid and as dexamethasone in this model. This inhibition of leukotriene secretion could partially explain the in-vivo antiallergic effects of Naaga.