2.B.52.  The N-acylethanolamine Proton Transport (NAE-PT) Family 

N-acylethanolamines (NAEs), N-arachidonoylethanolamine (anandamide) and N-oleoylethanolamine in nominally Ca2+-free media, are weakly protonophoric, manifested by dissipation of the transmembrane potential and stimulation of resting state respiration. The strongest action was exhibited by N-arachidonoylethanolamine, followed by N-oleoylethanolamine, whereas N-palmitoylethanolamine was almost inactive. These protonophoric effects were resistant to cyclosporin A (CsA) and were weaker than those of corresponding nonesterified fatty acids (Wasilewski et al. 2004). In uncoupled mitochondria, N-arachidonoylethanolamine and N-oleoylethanolamine partly inhibited mitochondrial respiration with glutamate and succinate but not with tetramethyl-p-phenylenediamine (TMPD) plus ascorbate as respiratory substrates. In mitochondria preloaded with small amounts of Ca2+, NAEs produced a much stronger dissipation of the membrane potential and a release of accumulated calcium, both effects being inhibited by CsA, indicative of opening of the mitochondrial permeability transition pore (PTP). Again, the potency of this action was N-arachidonoylethanolamine>N-oleoylethanolamine>N-palmitoylethanolamine. However, in spite of making the matrix space accessible to external [14C]sucrose, N-arachidonoylethanolamine and N-oleoylethanolamine resulted in only a limited swelling of mitochondria and diminished the rate of swelling produced by high Ca2+ load.



Wasilewski, M., M.R. Wieckowski, D. Dymkowska, and L. Wojtczak. (2004). Effects of N-acylethanolamines on mitochondrial energetics and permeability transition. Biochim. Biophys. Acta. 1657: 151-163.