Lysophospholipids do not directly modulate Na(+)-H+ exchange.

Lysophosphatidylcholine (LPC) has been reported to stimulate Na(+)-H+ exchange in rat cardiomyocytes. This action may be important in pathological conditions like ischemic injury where LPC is generated and Na(+)-H+ exchange activation is an important determinant of cardiac damage and dysfunction. It is unclear, however, if this stimulation of Na(+)-H+ exchange by LPC occurs through a direct action on the exchanger or through stimulation of a second messenger pathway. The purpose of the present investigation was to determine if lysolipids could directly affect Na(+)-H+ exchange. Purified cardiac sarcolemmal membranes were isolated and Na(+)-H+ exchange was measured by radioisotopic methods following addition of LPC. There were no effects of LPC on Na(+)-H+ exchange at LPC concentrations of < or = 100 microM at all reaction times examined. Lysophosphatidylethanolamine (LPE), lysophosphatidylserine (LPS), lysophosphatidylinositol (LPI) and lysoplasmenylcholine (LP(E)C) also did not alter Na(+)-H- exchange at all concentrations and reaction times examined. We conclude that any stimulatory effects of lysolipids on Na(+)-H+ exchange do not occur through a direct action on the exchanger or its membrane lipid environment and must occur through a second messenger pathway.