Lysophospholipids elevate [Ca2+]i and trigger exocytosis in bovine chromaffin cells

Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are responsible for many physiological functions, including angiogenesis, neuronal survival, and immunity. However, little is known about their effects in modulating the stimulus-secretion coupling in bovine chromaffin cells. The result of PCR showed that at least two receptors (S1P3 and LPA1) were expressed in bovine chromaffin cells. The elevation of [Ca2+]i by S1P was fast and sustaining; but the elevation by LPA was slow and transient. The EC50 for S1P and LPA in elevating the [Ca2+]i were 0.55 ± 0.01 and 0.54 ± 0.40 μM, respectively. This elevation could be totally blocked by thapsigargin, 2-APB, and U73122. Pertussis toxin pretreatment inhibited about half of the elevation in [Ca2+]i suggesting the involvement of Gi and other G-proteins. Repetitive [Ca2+]i elevations elicited by S1P, but not LPA, were inhibited by ryanodine. S1P was more effective than LPA in triggering exocytosis as measured by the changes in membrane capacitance. The whole-cell Ca2+ current was inhibited by both lysophospholipids but Na+ current was inhibited by S1P only. These results suggest the differential effects of LPA and S1P in releasing Ca2+ from the intracellular Ca2+ stores and modulating the stimulus-secretion coupling in bovine chromaffin cells.