The effects of stimulating protein kinase C on Cl- secretion across dog tracheal epithelium were investigated. The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), and the synthetic diacylglycerol, 1-oleoyl-2-acetylglycerol (OAG), which stimulate protein kinase C (PKC), both stimulated short-circuit current (I(sc)) with K(d) of 10 nM and 1 μM, respectively. In Cl--free solution, the increases in I(sc) were virtually abolished, suggesting that these compounds stimulate Cl- secretion, a hypothesis confirmed for TPA by measurement of 36Cl- fluxes. The stimulations of Cl- secretion were not sensitive to indomethacin, nor were cAMP levels elevated during stimulation. In addition to its transient stimulatory effect, TPA at high doses caused the eventual lowering of the base-line I(sc) and a block of subsequent stimulation by cAMP-mediated agonists. This was probably not the result of toxicity or an effect on adenylate cyclase or on cAMP-dependent protein kinase. Cell extracts from both cultured and native dog tracheal epithelial cells showed strong PKC activities. These results suggest that PKC may play a role in regulating Cl- secretion across dog tracheal epithelium.
|Original language||English (US)|
|Journal||American Journal of Physiology - Cell Physiology|
|State||Published - 1987|
ASJC Scopus subject areas
- Cell Biology
- Clinical Biochemistry