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Ca2+-independent form of protein kinase C may regulate Na+ transport across frog skin

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Summary

Activators of protein kinase C (PKC) stimulate Na− transport (J Na) across frog skin. We have examined the effect of Ca2+ on PKC stimulation ofJ Na. Both the phorbol ester 12-O-tetradecanoylglycerol (DiC8) were used as PKC activators. Blocking Ca2+ entry into the cytosol (either from external or internal stores) reduced the subsequent natriferic effect of the PKC activators. This negative interaction did not simply reflect saturation of activation of the apical Na+ channels, since the stimulations produced by blocking Ca2+ entry and adding cyclic AMP were simply additive.

The Ca2+ dependence of the natriferic effect could have reflected either a direct action of cytosolic Ca2+ on PKC or an indirect action on the final receptor site (the Na+ channel). To distinguish between these possibilities, the TPA- and phospholipid-dependent kinase activity of broken-cell preparations was assayed. The kinase activity was not stimulated by physiological levels of Ca2+, and in fact was inhibited at millimolar concentrations of Ca2+.

We conclude that the effects of Ca2+ on the natriferic response to PKC activators are indirect. Reducing cytosolic uptake of Ca2+ may have stimulated Na+ transport by a chemical modification of the apical channels observed in other tight epithelia. The usual stimulation of Na+ transport produced by PKC activators in frog skin may reflect the operation of a nonconventional form of PKC. This enzyme is Ca2+ independent and seems related to thenPKC or PKCε observed in other systems.

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  1. The Wistar Institute, University of Pennsylvania, 19104, Philadelphia, Pennsylvania

    Kenneth George & Thomas G. O'Brien

  2. Department of Physiology, University of Pennsylvania, 19104, Philadelphia, Pennsylvania

    Mortimer M. Civan, Allison Oler & Kim Peterson-Yantorno

  3. Department of Medicine, University of Pennsylvania, 19104, Philadelphia, Pennsylvania

    Mortimer M. Civan

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  1. Mortimer M. Civan
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Civan, M.M., Oler, A., Peterson-Yantorno, K. et al. Ca2+-independent form of protein kinase C may regulate Na+ transport across frog skin. J. Membrain Biol. 121, 37–50 (1991). https://doi.org/10.1007/BF01870649

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