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Discrimination between plasma membrane and intracellular target sites of sphingosylphosphorylcholine.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 1998 Jul 31; Vol. 354 (1), pp. 113-22. - Publication Year :
- 1998
-
Abstract
- On the background of the emerging concept of G protein-coupled sphingolipid receptors, Ca2+ mobilization by sphingosylphosphorylcholine (SPPC) in intact cells and SPPC-induced Ca2+ release in permeabilized cells, both occurring at similar, micromolar concentrations, were characterized and compared. In intact human embryonic kidney (HEK-293) cells, SPPC rapidly increased [Ca2+]i by mobilization of Ca2+ from thapsigargin-sensitive stores. In saponin-permeabilized HEK-293 cells, SPPC released stored Ca2+, in a manner similar to but independent of inositol 1,4,5-trisphosphate. Only the action of SPPC on intact cells, but not that in permeabilized cells, was, at least in part, sensitive to pertussis toxin. In addition and most important, Ca2+ release by SPPC in permeabilized cells was not stereoselective, whereas in intact cells only the naturally occurring D-erythro-SPPC, but not L-threo-SPPC, increased [Ca2+]i. Stereoselectivity of SPPC-induced [Ca2+]i increase was also demonstrated in bovine aortic endothelial cells. In conclusion, Ca2+ mobilization by SPPC in intact cells is independent of the previously described SPPC-gated Ca2+ channel on endoplasmic reticulum but probably mediated by a membrane sphingolipid receptor. Thus, SPPC can regulate Ca2+ homeostasis by acting apparently at two cellular targets, which exhibit clearly distinct recognition patterns.
- Subjects :
- Animals
Binding Sites
Calcium metabolism
Cattle
Cell Membrane drug effects
Cell Membrane Permeability drug effects
Cells, Cultured
Endothelium, Vascular cytology
Endothelium, Vascular drug effects
Endothelium, Vascular metabolism
Humans
Kidney cytology
Kidney drug effects
Kidney metabolism
Phosphorylcholine pharmacology
Receptors, Cell Surface drug effects
Receptors, Cell Surface metabolism
Saponins pharmacology
Sphingolipids metabolism
Sphingosine pharmacology
Stereoisomerism
Phosphorylcholine analogs & derivatives
Sphingosine analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 354
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 9726638
- Full Text :
- https://doi.org/10.1016/s0014-2999(98)00436-1