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A Role for G Protein‐Coupled Lysophospholipid Receptors in Sphingolipid‐Induced Ca 2+ Signaling in MC3T3‐E1 Osteoblastic Cells
Author(s) -
Lyons Jeremy M.,
Karin Norman J.
Publication year - 2001
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2001.16.11.2035
Subject(s) - lysophosphatidic acid , receptor , pertussis toxin , sphingosine , microbiology and biotechnology , sphingolipid , endoplasmic reticulum , biology , sphingosine 1 phosphate , second messenger system , g protein coupled receptor , signal transduction , g protein , biochemistry
Sphingolipids have been proposed to modulate cell function by acting as intracellular second messengers and through binding to plasma membrane receptors. Exposure of MC3T3‐E1 osteoblastic cells to sphingosine (SPH), sphingosine‐1‐phosphate (SPP), or sphingosylphosphorylcholine (SPC) led to the release of Ca 2+ from the endoplasmic reticulum (ER) and acute elevations in cytosolic‐free Ca 2+ ([Ca 2+ ] i ). Desensitization studies suggest that SPP and SPC bind plasma membrane endothelial differentiation gene ( Edg ) receptors for lysophosphatidic acid (LPA). Consistent with the coupling of Edg receptors to G proteins, SPP‐ and SPC‐induced Ca 2+ signaling was inhibited by pretreatment of the cells with pertussis toxin (PTx). Of the Edg receptors known to bind SPH derivatives in other cell types, MC3T3‐E1 cells were found to express transcripts encoding Edg ‐1 and Edg ‐5 but not Edg ‐3, Edg ‐6, or Edg ‐8. In contrast to SPP and SPC, the ability of SPH to elicit [Ca 2+ ] i elevations was affected neither by prior exposure of cells to LPA nor by PTx treatment. However, LPA‐induced Ca 2+ signaling was blocked in MC3T3‐E1 cells previously exposed to SPH. Elevations in [Ca 2+ ] i were not evoked by SPP or SPC in cells treated with 2‐aminoethoxydiphenylborate (2‐APB), an inhibitor of inositol 1,4,5‐trisphosphate (IP 3 )‐gated Ca 2+ channels in the ER. No effect of 2‐APB was observed on SPH‐ or LPA‐induced [Ca 2+ ] i elevations. The data support a model in which SPP and SPC bind Edg ‐1 and/or Edg ‐5 receptors in osteoblasts leading to the release of Ca 2+ from the ER through IP 3 ‐gated channels.