Protein kinase C and phospholipase D activation in rat parotid glands.
We have previously demonstrated that muscarinic and alpha-adrenergic receptors regulated a phospholipase D (PLD) activity in parotid glands. Since phorbol 12-myristate, 13-acetate (PMA) induced production of phosphatidylethanol (PEt), a stable metabolite widely accepted as marker of PLD activation, we have investigated the role of protein kinase C (PKC) in PLD stimulation in parotid acini. We tested PKC inhibitors on PEt formation elicited by PMA, by muscarinic and adrenergic agents. Staurosporine and chelerythrine, which act on the catalytic domain of PKC, did not allow the attribution of a role for PKC in PLD activation. Indeed, staurosporine did not affect PMA-mediated PLD activity and chelerythrine showed an important non-specific effect, independent of PKC inhibition. On the other hand, calphostin C, which acts on the regulatory domain of PKC, affected PMA- and receptor-mediated PLD stimulation. We attributed this effect to PKC inhibition and we suggested PKC involvement in PLD regulation in parotid gland. Since only PKC inhibitor acting on the regulatory part of the enzyme affected PLD activity, we also suggested that PKC could be involved in PLD activation through a pathway independent of the phosphorylation mechanism.
Guillemain
I
I
Laboratoire de Biochimie des Transports Cellulaires, CNRS URA 1116, Université Paris-Sud, Orsay, France.
Rossignol
B
B
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines; D004789:Enzyme Activation / Q000187:drug effects; D020404:Glycerophospholipids; D008297:Male; D009281:Naphthalenes; D010306:Parotid Gland / Q000201:enzymology*; D010617:Phenanthridines / Q000494:pharmacology; D010712:Phosphatidic Acids / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D053119:Benzophenanthridines; D020404:Glycerophospholipids; D009281:Naphthalenes; D010617:Phenanthridines; D010712:Phosphatidic Acids; D011083:Polycyclic Compounds; C051521:phosphatidylethanol; C016299:chelerythrine; D011493:Protein Kinase C; D010739:Phospholipase D; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate