Modulation of excitability, membrane currents and survival of cardiac myocytes by N-acylethanolamines.

N-acylethanolamines (NAE) are endogenously produced lipids playing important roles in a diverse range of physiological and pathological conditions. In the present study, using whole-cell patch clamp technique, we have for the first time investigated the effects of the most abundantly produced NAEs, N-stearoylethanolamine (SEA) and N-oleoylethanolamine (OEA), on electric excitability and membrane currents in cardiomyocytes isolated from endocardial, epicardial, and atrial regions of neonatal rat heart. SEA and OEA (1-10µM) attenuated electrical activity of the myocytes from all regions of the cardiac muscle by hyperpolarizing resting potential, reducing amplitude, and shortening the duration of the action potential. However, the magnitudes of these effects varied significantly depending on the type of cardiac myocyte (i.e., endocardial, epicardial, atrial) with OEA being generally more potent. OEA and to a lesser extent SEA suppressed in a concentration-dependent manner currents through voltage-gated Na(+) (VGSC) and L-type Ca(2+) (VGCC) channels, but induced variable cardiac myocyte type-dependent effects on background K(+) and Cl(-) conductance. The mechanisms of inhibitory action of OEA on cardiac VGSCs and VGCCs involved influence on channels' activation/inactivation gating and partial blockade of ion permeation. OEA also enhanced the viability of cardiac myocytes by reducing necrosis without a significant effect on apoptosis. We conclude that SEA and OEA attenuate the excitability of cardiac myocytes mainly through inhibition of VGSCs and VGCC-mediated Ca(2+) entry. Since NAEs are known to increase during tissue ischemia and infarction, these effects of NAEs may mediate some of their cardioprotective actions during these pathological conditions.

N-stearoylethanolamine restores pancreas lipid composition in obesity-induced insulin resistant rats.

This study investigates the protective effect of N-stearoylethanolamine (NSE), a bioactive N-acylethanolamine , on the lipid profile distribution in the pancreas of obesity-induced insulin resistant (IR) rats fed with prolonged high fat diet (58% of fat for 6 months). The phospholipid composition was determined using 2D thin-layer chromatography. The level of individual phospholipids was estimated by measuring inorganic phosphorus content. The fatty acid (FA) composition and cholesterol level were investigated by gas-liquid chromatography. Compared to controls, plasma levels of triglycerides and insulin were significantly increased in IR rats. The pancreas lipid composition indicated a significant reduction of the free cholesterol level and some phospholipids such as phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), phosphatidylinositol (PtdIns), phosphatidylserine (PtdSer) compared to controls. Moreover, the FA composition of pancreas showed a significant redistribution of the main FA (18:1n-9, 18:2n-6, 18:3n-6 and 20:4n-6) levels between phospholipid, free FA, triglyceride fractions under IR conditions that was accompanied by a change in the estimated activities of Δ9-, Δ6-, Δ5-desaturase. Administration of N-stearoylethanolamine (NSE, 50 mg/kg daily per os for 2 weeks) IR rats triggered an increase in the content of free cholesterol, PtdCho and normalization of PtdEtn, PtdSer level. Furthermore, the NSE modulated the activity of desaturases, thus influenced FA composition and restored the FA ratios in the lipid fractions. These NSE-induced changes were associated with a normalization of plasma triglyceride content, considerable decrease of insulin and index HOMA-IR level in rats under IR conditions.