Effects of N-acylethanolamines on mitochondrial energetics and permeability transition.
Effects of N-acylethanolamines (NAEs): N-arachidonoylethanolamine (anandamide), N-oleoylethanolamine and N-palmitoylethanolamine, on energy coupling and permeability of rat heart mitochondria were investigated. In nominally Ca2+-free media, these compounds exerted a weak protonophoric effect 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 much weaker than those of corresponding nonesterified fatty acids. 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 for 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
Michał
M
Department of Cellular Biochemistry, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Pasteura 3, PL-02-093 Warsaw, Poland.
Wieckowski
Mariusz R
MR
Dymkowska
Dorota
D
Wojtczak
Lech
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004983:Ethanolamines / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D051381:Rats
D004983:Ethanolamines; D002118:Calcium