Hydrolysis of anandamide and eicosapentaenoic acid ethanolamide in mouse splenocytes

摘要

Anandamide hydrolysis in mouse splenocytes has been studied using tritiated anandamide analogs labelled in the acyl- or ethanolamide parts of the molecule. [~3H] anandamide undergoes rapid (t_(1/2) 2.5 min) uptake and hydrolysis to ethanolamine and arachidonic acid. The anandamide hydrolysis in splenocytes is sensitive to inhibition by phenylmethylsulfonyl fluoride, and we assume that the observed activity is due to fatty acid amide hydrolase, which inactivates anandamide are amidohydrolase substrates as well. Fatty acids derived from hydrolytic cleavage of acylethanolamines undergo rapid oxidation by splenocytic lipoxygenase, yielding corresponding 12-hydroxy derivatives. Oxygenated ethanolamide derivatives were never detected. The data suggest that polyenoic fatty acid ethanolamides are metabolic precursors of eicosanoids in splenocytes, and that amide bond hydrolysis is a key point in switching of biological activity spectra between endocannabinoids and oxylipins.