4α-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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.