Marked activation of the N-acylphosphatidylethanolamine-hydrolyzing phosphodiesterase by divalent cations.

N-Acylethanolamines including anandamide (an endogenous ligand for cannabinoid receptors) are released from N-acylphosphatidylethanolamine (N-acyl-PE) by the catalysis of a phosphodiesterase of the phospholipase D type. The enzyme was solubilized from the particulate fractions of rat heart with the aid of octyl glucoside, and partially purified by anion-exchange chromatography. The enzyme hydrolyzed N-palmitoyl-PE with a specific activity of 17 nmol/min/mg protein at 37 degrees C. The enzyme activity increased dramatically up to 30-fold by millimolar order of Ca(2+). Ca(2+) could be replaced with other divalent cations such as Co(2+), Mg(2+), Mn(2+), Ba(2+), Sr(2+) and Ni(2+). The hydrolysis of N-arachidonoyl-PE (a precursor of anandamide) was also markedly stimulated by Ca(2+).