The alteration of rabbit skeletal sarcoplasmic reticulum function by N-acylethanolamine, a lipid associated with...

The ability of N-acylethanolamines (pharmacologically active lipid metabolites which accumulate in canine myocardium during experimentally induced infarctions) to alter Ca2+ fluxes in a biological membrane system was studied using sarcoplasmic reticulum vesicles prepared from rabbit skeletal muscle. The effects of two N-acylethanolamines, the N-oleyl and N-lauryl derivatives, were compared to those of the lipophilic drugs, dibucaine and propranolol. The rate and extent of Ca2+ sequestration, Ca2+-Mg2+-ATPase activity and retention time of Ca2+ by the vesicles were all stimulated at low concentrations of the four compounds studied and inhibited at higher concentrations. The stoichiometry between Ca2+-pumping rates and ATPase activity was partially "uncoupled" indicating that both the calcium pump and the membrane permeability were affected by the drugs. However, although all four compounds exhibited the same qualitative behavior, the effects of the two N-acylethanolamines were more pronounced than dibucaine and propranolol and occurred at much lower concentrations. These results suggest that the N-acylethanolamines may have important physiological effects in the myocardium and, at least at lower concentrations, stimulate myocardial contractility by increasing the rate of calcium flux across the sarcoplasmic reticulum.