4alpha-Phorbol negates the inhibitory effects of phorbol-12-myristate-13-acetate on human cilia and alters the phosphorylation of PKC.
In medium 199, ciliary beat frequency (CBF) in human nasal epithelium declines to 60% of baseline by 2 h and 1 nM phorbol-12-myristate-13-acetate (PMA) doubles the rate of decline by activating protein kinase C (PKC). We find that a reported negative control for PMA, 4alpha-phorbol (1 pM-1 nM)+/-1 nM PMA, not only maintains CBF at baseline, but arrests a pre-existing PMA-induced decline in CBF and alters the profile of multiple phosphorylated PKC species. Thus, 4alpha-phorbol not only potently prevents PMA from inhibiting CBF but also has potent effects on the phosphorylation of PKC.
Mwimbi
Xowi K M S
XK
Tayside Institute of Child Health, Ninewells Hospital and Medical School, University of Dundee, UK.
Muimo
Richmond
R
Treharne
Kate J
KJ
Sijumbila
Gibson
G
Green
Michael
M
Mehta
Anil
A
D015153:Blotting, Western; D002478:Cells, Cultured; D002923:Cilia / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007202:Indicators and Reagents; D009297:Nasal Mucosa / Q000187:drug effects / Q000201:enzymology; D010704:Phorbols / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D007202:Indicators and Reagents; D010704:Phorbols; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; C033085:phorbol