Sphingosine regulates Ca(2+)-ATPase and reloading of intracellular Ca2+ stores in the pancreatic acinar cell.
The purpose of present study was to examine the effects of sphingosine on cellular Ca2+ transports using dispersed rat pancreatic acini. The results demonstrated that sphingosine had a specific effect to inhibit Ca2+ uptake into the cell's agonist-sensitive pool as well as inhibiting microsomal Ca(2+)-ATPase. The ability of sphingosine to inhibit Ca2+ uptake resulted in both augmentation of Ca2+ release from the pool by inositol 1,4,5-trisphosphate (IP3) and conversion of the Ca2+ release by inositol 1,4,5-trisphosphate from a transient response to a sustained response. Furthermore, by preventing Ca2+ pool refilling sphingosine mimicked the effect of the agonist, carbachol, to maintain an increased [Ca2+]i during sustained stimulation. These results suggest that regulation of Ca(2+)-ATPase by sphingosine or a sphingosine-like agent mediates some of the effects of agonist on cell Ca2+ transports.
Pandol
S J
SJ
Department of Veterans Affairs Medical Center, San Diego, CA 92161.
Schoeffield-Payne
M S
MS
Gukovskaya
A S
AS
Rutherford
R E
RE
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D016257:Fura-2; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012844:Sincalide / Q000494:pharmacology; D013110:Sphingosine / Q000494:pharmacology*
D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D000252:Calcium-Transporting ATPases; D012844:Sincalide; D013110:Sphingosine; D002118:Calcium; D016257:Fura-2