Accumulation of VariousN-Acylethanolamines IncludingN-Arachidonoylethanolamine (Anandamide) in Cadmium Chloride-Administered Rat Testis

Changes in the levels of various molecular species ofN-acylethanolamine in CdCl2-administered rat testis were examined. We found that the levels of variousN-acylethanolamines including anandamide (N-arachidonoylethanolamine), an endogenous cannabinoid receptor ligand, were dramatically increased in CdCl2-admin-istered rat testis. Such changes were particularlyprominent for saturated and monoenoic species such asN-palmitoyl species (39-fold at 9 h) andN-stearoyl species (21-fold at 9 h), compared with unsaturated fatty acid-containing species such as anandamide (5-fold at 9 h). Noticeably, increased levels were observed of not onlyN-acylethanolamines but also several species ofN-acylphosphatidylethanolamine, potential precursors forN-acylethanolamines. We confirmed that the rat testis microsomal fraction contains phosphodiesterase activity catalyzing the release ofN-acylethanolamine fromN-acylphosphatidylethanolamine and transacylase activity catalyzing the formation ofN-acylphosphatidylethanolamine from phosphatidylethanolamine and phosphatidylcholine. These enzyme activities were not dramatically different in the microsomal fraction obtained from CdCl2-administered rat testis compared with that in the case of control rat testis, at least when estimated in cell-free assay systems, suggesting that the accessibility of the substrates to the enzymes may be increased in CdCl2-administered rat testis to generate a large amount ofN-acylethanolamine. Possible pathophysiological implications of the augmented generation ofN-acylethanolamine including anandamide in CdCl2-administered rat testis were discussed.