The forskolin-induced opening of tight junctions in xenopus gallbladder epithelium is mediated by protein kinase C

The effects of protein kinase A (PKA)-mediated and protein kinase C (PKC)-mediated stimulation on the tight junctions of the moderately tight Xenopus gallbladder epithelium have been investigated. Transepithelial impedance and DC voltage divider ratio measurements in Ussing-type chambers were used to calculate the cell membrane and fight junction resistances in the stimulated state. Under control conditions the TE resistance was used as a lowest estimate of fight junction resistance. Stimulation of PKA by forskolin and theophyllin as well as stimulation of PKC by phorbol dibutyrate lowered the TE resistance mainly via the reduction of die fight junctional resistance. PKA stimulation opened, in addition, an apical Cl--selective conductance. The paracellular pathway activated by PKA or PKC did not discriminate between small anions and cations. The effects of PKA stimulation could be blocked by the selective inhibition of PKA (with H89) or of PKC (with bisindolylmaleimide). By contrast, the PKC-evoked effects were insensitive to H89, showing that the effects of PKA on the paracellular pathway were mediated by PKC.