Phosphatidic acid promotes phosphoinositide metabolism and DNA synthesis in cultured cortical astrocytes.
The addition of exogenous phosphatidic acid (PA) to cultured cortical astrocytes prelabelled with [3H]inositol resulted in the accumulation of intracellular [3H]inositol phosphates (IP) in a concentration-dependent (EC50 = 20 microM) manner. Analysis of the individual IPs formed following a PA challenge revealed a rapid but transient generation of [3H]inositol trisphosphate (IP3) indicating the involvement of phosphatidylinositol 4,5-bisphosphate (PIP2) breakdown in this response a fact which was confirmed when the recovery of radiolabel in membrane phosphoinositides was assessed. PA's ability to stimulate IP3 accumulation was found to be dependent upon its acyl-chain length. Dioleoyl-PA (C18:1) was equally as effective as PA from egg yolk lecithin in this respect whilst dipalmitoyl-PA (C16:0) was less so and dimyristoyl-PA (C14:0) and dilauroyl-PA (C12:0) were without effect. In subconfluent, serum-deprived cultures, PA was found to increase DNA synthesis following a 48 h exposure period. This effect was observed over the same concentration range used to measure phosphoinositide breakdown and was found to be mediated by the activation of protein kinase C. As with its effect on phosphoinositide metabolism, PA's ability to promote DNA synthesis was correlated with its acyl-chain length. These data show that PA is capable of stimulating both phosphoinositide metabolism and DNA synthesis in cultured astrocytes possibly via the activation of specific membrane receptors. However, the precise relationship between these events remains to be elucidated.
Pearce
B
B
Pharmacology Department, School of Pharmacy, London, U.K.
Jakobson
K
K
Morrow
C
C
Murphy
S
S
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis*; D010712:Phosphatidic Acids / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats
D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D004247:DNA