Enhancing effect of wortmannin on muscarinic stimulation of phospholipase D in rat pheochromocytoma PC12 cells.
Wortmannin, a specific inhibitor of myosin light chain kinase (MLCK), enhanced carbachol-induced formation of [3H]phosphatidylethanol ([3H]PEt), a marker of phospholipase D (PLD) activity, in [3H]palmitic acid-labeled PC12 cells. The apparent EC50 value was 1.5 microM, and the effect was maximal at 3 microM and slightly attenuated at higher concentration. Wortmannin alone had no significant effect on [3H]PEt formation. The enhancing effect of wortmannin was observed at the initial increasing phase of [3H]PEt formation but not at the subsequent plateau phase. Wortmannin enhanced also phorbol ester-induced PLD activation. Although the precise mechanism remains to be clarified, these results suggest that MLCK may be involved in PLD regulation in PC12 cells.
Kanoh
H
H
Department of Biochemistry, Gifu University School of Medicine, Japan.
Ohbayashi
H
H
Matsuda
Y
Y
Nonomura
Y
Y
Nozawa
Y
Y
D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology*; D004789:Enzyme Activation; D020404:Glycerophospholipids; D007700:Kinetics; D016716:PC12 Cells; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D000077191:Wortmannin
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D020404:Glycerophospholipids; D010712:Phosphatidic Acids; C051521:phosphatidylethanol; D002217:Carbachol; D010739:Phospholipase D; D000077191:Wortmannin