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 (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+/-0.40microM, 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.
Pan
Chien-Yuan
CY
Institute of Zoology, National Taiwan University, Taipei, Taiwan, ROC. cypan@ntu.edu.tw
Lee
Hsinyu
H
Chen
Chia-Lin
CL
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D002395:Catecholamines / Q000378:metabolism; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002469:Cell Separation; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005089:Exocytosis / Q000187:drug effects*; D015544:Inositol 1,4,5-Trisphosphate / Q000037:antagonists & inhibitors / Q000502:physiology; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000494:pharmacology*; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012433:Ryanodine / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000096:biosynthesis; D019284:Thapsigargin / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002395:Catecholamines; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D026941:Sodium Channel Blockers; D012433:Ryanodine; C060506:sphingosine 1-phosphate; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D013110:Sphingosine; C032881:lysophosphatidic acid; D002118:Calcium