Protein kinase C down-regulation in astrocytes: differential effects on agonist-stimulated inositol phosphate accumulation.
Prolonged phorbol ester treatment abolished protein kinase C (PKC) activity for over 48 h in cortical astrocyte cultures. Receptor-stimulated inositol phospholipid breakdown in these cultures subsequent to PKC depletion produced either enhanced, depressed or unchanged responses depending upon the agonist used. Noradrenaline-, ATP-, histamine- and glutamate-evoked [3H]-inositol phosphate accumulations were potentiated to varying degrees in PKC-depleted cultures whilst those evoked by carbachol and NaF were reduced and unchanged respectively. Analysis of the individual metabolites of inositol phospholipid metabolism formed in response to noradrenaline in PKC-depleted astrocytes revealed potentiated accumulations of radiolabelled glycerophosphoinositol (GPI), inositol monophosphate (IP1) and inositol bisphosphate (IP2) but not inositol trisphosphate (IP3) when compared to controls. Under the same conditions, accumulations of radiolabelled IP1 and IP2 were reduced and those of GPI and IP3 unchanged in carbachol-treated cultures. These results suggest that astrocyte receptors coupled to inositol phospholipid metabolism are differentially regulated by PKC.
Pearce
B
B
Department of Pharmacology, School of Pharmacy, London, U.K.
Murphy
S
S
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006632:Histamine / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D007700:Kinetics; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D012969:Sodium Fluoride / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D005971:Glutamates; D007295:Inositol Phosphates; D018698:Glutamic Acid; D006632:Histamine; D000255:Adenosine Triphosphate; D002217:Carbachol; D012969:Sodium Fluoride; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine