Mg2+ modulates membrane sphingolipid and lipid second messenger levels in vascular smooth muscle cells

In vitro studies with smooth muscle cells from rat aorta and dog cerebral b lood vessels indicate that variation in free Mg2+, within the pathophysiolo gical range of Mg2+ concentrations, found in human serum, causes sustained changes in membrane phospholipids and lipid second messengers. Incorporatio n of [H-3]palmitic acid into phosphatidylcholine (PC) and sphingomyelin (SM ) was altered within 15-30 min after modifying the extracellular Mg2+ ion l evel ([Mg2+](o)). Decreased Mg2+ produced a fall in both [H-3]SM and [H-3]P C over the first 2 h, After an 18-h incubation, the [H-3]PC/[H-3]SM ratio c hanged from about 20:1 to about 50:1. Increased [Mg2+](o) resulted in a 2- to 3-fold increase in [H-3]SM compared to only a small increase in [H-3]PC over the same period. There was a reciprocal relationship between [H-3]cera mide and [H-3]1,2-DAG levels with highest [H-3]ceramide and lowest [H-3]-1, 2-DAG levels seen at lowest [Mg2+](o). Tbe results indicate that a fall in extracellular ionized Mg2+ concentration produces a rapid and sustained dec rease in membrane sphingomyelin and a moderate rise in intracellular cerami de, A major effect of lowering [Mg2+](o) appears to be a down-regulation of SM synthase, The increased membrane SM content and a concomitant decrease in cell ceramide, in the presence of elevated [Mg2+](o), may be relevant to the apparent protective role of adequate Mg intake on vascular function in humans. (C) 1998 Federation of European Biochemical Societies.