Norepinephrine-induced 1,2-diacylglycerol accumulation and change in its fatty acid composition in the isolated perfused rat heart

Abstract

Phosphoinositide hydrolysis is elicited by alpha-adrenoceptor stimulation in the myocardium, resulting in the generation of 1,2-diacylglycerol by the direct activation of phospholipase C. However, the physiological role of 1,2-diacylglycerol accumulation in the heart has been largely unexplored. Therefore, we studied the effects of norepinephrine on the accumulation of 1,2-diacylglycerol and its fatty acid composition, as well as its function in isolated perfused rat hearts. A 30 min perfusion with norepinephrine following a stabilization period of 25 min caused increases of 68% and 57% in 1,2-diacylglycerol levels in the heart at 10(-6) M and 5 x 10(-6) M, respectively, compared to controls. Analysis of its fatty acid composition showed a significant elevation in the percentages of 18:2 and 20:4 although the absolute amounts of these increases in fatty acids were relatively low when compared to the elevation in the total amount of 1,2-diacylglycerol. The change in contractility was not consistently related to an increase in 1,2-diacylglycerol. These results indicate that the increase in 1,2-diacylglycerol level in response to norepinephrine perfusion was accompanied by a change in fatty acid composition of 1,2-diacylglycerol.