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

Abstract Changes in the levels of various molecular species of N -acylethanolamine in CdCl 2 -administered rat testis were examined. We found that the levels of various N -acylethanolamines including anandamide ( N -arachidonoylethanolamine), an endogenous cannabinoid receptor ligand, were dramatically increased in CdCl 2 -admin-istered rat testis. Such changes were particularlyprominent for saturated and monoenoic species such as N -palmitoyl species (39-fold at 9 h) and N -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 only N -acylethanolamines but also several species of N -acylphosphatidylethanolamine, potential precursors for N -acylethanolamines. We confirmed that the rat testis microsomal fraction contains phosphodiesterase activity catalyzing the release of N -acylethanolamine from N -acylphosphatidylethanolamine and transacylase activity catalyzing the formation of N -acylphosphatidylethanolamine from phosphatidylethanolamine and phosphatidylcholine. These enzyme activities were not dramatically different in the microsomal fraction obtained from CdCl 2 -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 CdCl 2 -administered rat testis to generate a large amount of N -acylethanolamine. Possible pathophysiological implications of the augmented generation of N -acylethanolamine including anandamide in CdCl 2 -administered rat testis were discussed.