Regulation of phosphoinositide hydrolysis in cultured astrocytes by sphingosine and psychosine.
The effects of sphingosine and psychosine on phosphoinositide hydrolysis in primary cultured astrocytes were determined. Exposure to sphingosine produced a dose-dependent stimulation of phosphoinositide hydrolysis requiring the presence of external Ca++ for optimal activity. The addition of 10 microM norepinephrine resulted in a stimulation additional to that with sphingosine. The alpha 1-antagonist prazosin completely inhibited norepinephrine-induced phosphoinositide hydrolysis but had no effect on that produced by sphingosine. Psychosine (108 microM), when co-incubated with sphingosine, produced complete inhibition of sphingosine-induced phosphoinositide hydrolysis at all doses of sphingosine tested (33-668 microM). Likewise, psychosine totally inhibited norepinephrine-induced phosphoinositide hydrolysis. The protein kinase C inhibitor staurosporine (1 microM) had no effect on sphingosine-induced phosphoinositide hydrolysis. These findings suggest that lysosphingolipids such as sphingosine and psychosine may play an important role in the regulation of phosphoinositide turnover in astrocytes by a mechanism dependent on extracellular Ca++ and independent of the alpha 1-adrenergic receptor and protein kinase C.
Ritchie
T
T
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles 90024-1759.
Rosenberg
A
A
Noble
E P
EP
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011609:Psychosine / Q000494:pharmacology*; D051381:Rats; D013110:Sphingosine / Q000494:pharmacology*; D019311:Staurosporine
D000470:Alkaloids; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011609:Psychosine; D004533:Egtazic Acid; D011493:Protein Kinase C; D019311:Staurosporine; D013110:Sphingosine; D002118:Calcium; D009638:Norepinephrine