Protein kinase c in intracellular ph regulation in alveolar type ii
cells.
Wadsworth, Sandra, Ai-Min Wu, Alan Spitzer, and Avinash Chander.
Department of Pediatrics, Division of Neonatology, Jefferson
Medical College, Thomas Jefferson University, Philadelphia, PA
19104
APStracts 3:0036L, 1996.
The Na+/H+ exchanger and Na+/HCO3- cotransporter have been implicated
in regulation of intracellular pH (pHi) in alveolar type II cells.
This study demonstrates that activation of protein kinase C (PKC)
stimulates both of these ion transporters in type II cells. Treatment
of type II cells with 80 nM phorbol 12 - myristate 13 - acetate (PMA)
increased the resting pHi in a time-dependent manner. Compared to
control cells, the rates of recovery from an acid load increased with
PMA treatment, reaching a maximum at 15 min and returned to control
levels by 3 h. The PMA-stimulated changes in recovery rate were
sensitive to H - 7, a PKC inhibitor. For PMA treatment up to 2 h,
these recoveries were also sensitive to dimethylamiloride (DMA), an
inhibitor of Na+/H+ exchanger activity, and to HCO3-, suggesting
activation of both the Na+/H+ exchanger and the Na+/HCO3-
cotransporter. After prolonged (3 h) treatment with PMA, however, the
recovery was insensitive to DMA but was sensitive to HCO3-,
suggesting that the Na+/H+ exchanger was no longer active and that
most of the recovery was mediated by the Na+/HCO3- cotransporter. PMA
treatment also altered the Na+ kinetics of the recovery from an acid
load with respect to Km and Vmax, suggesting protein modifications of
each transporter. We suggest that PKC activation in type II cells
results in acute and long term changes in pHi regulatory mechanisms
mediated by the Na+/H+ exchanger and by the Na+/HCO3- cotransporter.
Received 6 July 1995; accepted in final form 26 February 1996.
APS Manuscript Number L196-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 20 March 96