Lysophospholipids elevate [Ca 2+] i and trigger exocytosis in bovine chromaffin cells

Abstract

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 (S1P 3 and LPA 1) were expressed in bovine chromaffin cells. The elevation of [Ca 2+] i by S1P was fast and sustaining; but the elevation by LPA was slow and transient. The EC 50 for S1P and LPA in elevating the [Ca 2+] 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 [Ca 2+] i suggesting the involvement of G i and other G-proteins. Repetitive [Ca 2+] 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 Ca 2+ 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 Ca 2+ from the intracellular Ca 2+ stores and modulating the stimulus-secretion coupling in bovine chromaffin cells.