Interactions of TPA and insulin on Na+ transport across frog skin.
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.
Civan
M M
MM
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia 19104.
Peterson-Yantorno
K
K
George
K
K
O'Brien
T G
TG
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D004553:Electric Conductivity; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008433:Mathematics; D008564:Membrane Potentials / Q000187:drug effects; D009092:Mucous Membrane / Q000187:drug effects / Q000502:physiology; D011894:Rana pipiens; D012867:Skin / Q000187:drug effects; D012879:Skin Physiological Phenomena; D012964:Sodium / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D001127:Arginine Vasopressin; D000584:Amiloride; D012964:Sodium; D013755:Tetradecanoylphorbol Acetate