AJP - Cell Physiology, Vol 253, Issue 6 C828-C834, Copyright © 1987 by American Physiological Society

ARTICLES

Effect of phorbol ester and calcium ionophore on chloride secretion in canine tracheal epithelium

M. J. Welsh
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.

The control of Cl- secretion was examined by two of the terminal events in the phosphoinositide regulatory pathway: activation of protein kinase C and an increase in cell Ca2+. The phorbol ester phorbol 12-myristate 13-acetate (PMA), which activates protein kinase C, stimulated Cl- secretion in both native and cultured monolayers of tracheal epithelium. Approximately 1.5 nM of mucosal PMA was required for half-maximal stimulation. Stimulation was not dependent on prostaglandin production nor was it accompanied by an increase in cellular levels of cAMP. Although the maximal rate of PMA-induced Cl- secretion was less than that induced by cAMP, there was a synergistic effect between PMA and forskolin, an agent that activates adenylate cyclase. The response to PMA was at least partly transient and PMA may also attenuate Cl- secretion under some circumstances. Thus the response to PMA, and presumably protein kinase C activation, may be complex. An increase in cell Ca2+ produced by addition of the Ca2+ ionophore A23187 also stimulated Cl- secretion. However, the effect was at least partly indirect. A23187 enhanced prostaglandin E2 production and the prostaglandin synthesis inhibitor, indomethacin, blocked A23187-induced secretion in native epithelia and attenuated the effect of A23187 in cultured monolayers. These results indicate the presence of a non-cAMP-dependent regulatory pathway capable of controlling Cl- secretion in tracheal epithelium. Activation of protein kinase C may stimulate secretion directly or modulate the response to cAMP. An increase in cell Ca2+ may stimulate secretion at least partly by stimulating endogenous prostaglandin production.

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