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AJP - Cell Physiology, Vol 256, Issue 3 C569-C578, Copyright © 1989 by American Physiological Society
ARTICLES |
M. M. Civan, K. Peterson-Yantorno, K. George and T. G. O'Brien
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
The phorbol ester 12-O-tetradecanoylphorbol 13-acetate (TPA) activates protein kinase C (PKC) and produces an early stimulation of Na+ transport across frog skin. The ionic basis for this stimulation was studied with combined transepithelial and intracellular electrical measurements. In an initial series of experiments, TPA approximately doubled the amiloride-sensitive short-circuit current (ISC), apical Na+ permeability (PapNa), and apical membrane conductance without affecting the basolateral membrane conductance. The apical effects led to a marked depolarization of the short-circuited skin and a small increase in intracellular Na+ concentration. TPAs increase of PapNa was sufficient to explain the stimulation of basolateral Na+ transport when both the voltage and substrate dependence of the pump were taken into account. After the early stimulation, TPA later depressed ISC. Added at this point (congruent to 1-2 h after TPA administration), insulin had no effect on ISC, whereas a partial response to vasopressin was still observed. Measured either early or late after TPA addition, the phorbol ester reduced insulin binding by congruent to 40%. Insofar as 60% of the specific binding is retained, the abolishment of insulin's natriferic response is unlikely to result from the TPA-induced reduction in hormonal binding. The data provide further support for the concept that activation of PKC produces an early stimulation of Na+ transport by increasing apical Na+ permeability, and that part of insulin's natriferic effect may be mediated by PKC activation.
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W. J. Els, X. Liu, and S. I. Helman Differential effects of phorbol ester (PMA) on blocker-sensitive ENaCs of frog skin and A6 epithelia Am J Physiol Cell Physiol, July 1, 1998; 275(1): C120 - C129. [Abstract] [Full Text] [PDF] |
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