title: Regulation of epithelial Na+ permeability by protein kinase C is tissue specific.
abstract: Protein kinase C (PKC) is a major regulator of a broad range of cellular functions. Activation of PKC has been reported to stimulate Na+ transport across frog skin epithelium by increasing the apical Na+ permeability. This positive natriferic response has not been observed with other epithelial preparations, and could reflect the specific experimental conditions of different laboratories, or species or organ specificity of the response to PKC. In the present study, measurements were conducted with skins and urinary bladders from the same animals of two different species. The PKC activator TPA uniformly increased the transepithelial Na+ transport (measured as amiloride-sensitive short-circuit current, ISC, across skins from Rana temporaria and Bufo marinus, and inhibited ISC across bladders from the same animals. Inhibitors of PKC (staurosporine, H-7 and chelerythrine) partially blocked the TPA-induced stimulation of ISC across frog skin. The specificity of the PKC response by amphibian skin could have reflected an induction of moulting, similar to that observed with aldosterone. However, light micrographs of paired areas of frog skin revealed no evidence of the putative moulting. Separation of stratum corneum from the underlying stratum granulosum could be detected following application of aldosterone. We conclude that the effect of PKC on epithelial Na+ channels is organ, and not species specific. The stimulation of Na+ permeability in amphibian skin does not arise from sloughing of the stratum corneum. These observations are consistent with the hypothesis that the natriferic action arises from the calcium-independent isozyme of PKC previously detected in frog skin.
authors.affiliation: Department of Physiology, University of Pennsylvania, Philadelphia, PA 19104-6085, USA.
authors.forename: M L
authors.initials: ML
authors.lastname: Chalfant
authors.forename: J M
authors.initials: JM
authors.lastname: Civan
authors.forename: K
authors.initials: K
authors.lastname: Peterson-Yantorno
authors.forename: D R
authors.initials: DR
authors.lastname: DiBona
authors.forename: T G
authors.initials: TG
authors.lastname: O'Brien
authors.forename: M M
authors.initials: MM
authors.lastname: Civan
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000450:Aldosterone / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines; D001692:Biological Transport / Q000187:drug effects; D002024:Bufo marinus; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D009928:Organ Specificity; D010617:Phenanthridines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011892:Rana catesbeiana; D011894:Rana pipiens; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D012964:Sodium / Q000378:metabolism*; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology*
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010617:Phenanthridines; D010879:Piperazines; D000450:Aldosterone; D000584:Amiloride; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D012964:Sodium; C016299:chelerythrine; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate