N-acetyl-sphingenine-1-phosphate is a potent calcium mobilizing agent.
Calcium mobilization induced by phosphorylated sphingoid bases was analyzed in calf pulmonary artery endothelial cells by confocal microscopy. A sphingenine-1-phosphate (SeP) analogue, N-acetyl-sphingenine-1-phosphate (N-C2-SeP), exogenously added to these cells, caused a fast and transient intracellular rise in calcium and was as potent as SeP. A minimal concentration of 0.6 nM for N-C2-SeP versus 1 nM for SeP was determined. The N-C2-SeP-induced Ca2+-signaling, like the response to SeP, was due to a release from thapsigargin-sensitive, ryanodine-insensitive, intracellular Ca2+-stores and not to a Ca2+-influx. N-C2-SeP can be considered as a truncated ceramide-phosphate, a lipid already reported to be mitogenic (Gomez-Munoz, A., Duffy, P.A., Martin, A., O'Brien, L., Byun, H.S., Bittman, R. and Brindley, D.N. (1995) Mol. Pharmacol. 47, 833-839), an effect that might be secondary to Ca2+-mobilization.
Gijsbers
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Departement Moleculaire Celbiologie, Afdeling Farmakologie, Katholieke Universiteit Leuven, Belgium.
Mannaerts
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Himpens
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Van Veldhoven
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D000818:Animals; D020013:Calcium Signaling; D002417:Cattle; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D018613:Microscopy, Confocal; D011651:Pulmonary Artery / Q000166:cytology; D012433:Ryanodine / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
C120365:N-acetylsphingenine-1-phosphate; C120366:sphingenine-1-phosphate; D012433:Ryanodine; C060504:dihydrosphingosine 1-phosphate; D019284:Thapsigargin; D013110:Sphingosine