Dual role of prostaglandins (PGE(2)) in regulation of channel density and open probability of epithelial Na+ channels in frog skin (R-pipiens)

Prostaglandins are important in signaling pathways involved in modulating the rates of Na+ transport in a diverse group of tissues possessing apical membrane epithelial channels. PGE(2) is known to cause either stimulation, inhibition or transient stimulatory changes of Na+ transport. We have continued our studies of frog skins that are known to respond to forskolin and PGE(2) with large steady-state increases of transport and have used noninvasive methods of blocker-induced noise analysis of Na+ channels to determine their channel densities (N-T) and open probabilities (P-o). In the absence of exogenous hormones, baseline rates of Na+ transport are especially high in scraped skins (R. pipiens pipiens) studied in the fall season of the year. Na+ transport was inhibited by indomethacin and by removal of the unstirred layers of the cerium (isolated epithelia) alone suggesting that PGE(2) is responsible for the sustained and elevated rates of transport in scraped skins. Changes of transport caused by indomethacin, forskolin or PGE(2) were unquestionably mediated by considerably larger changes of N, than compensatory changes of P-o. Since cAMP caused no change of P, in tissues pretreated with indomethacin, PGE(2) appears in this tissue to serve a dual role, increasing the steady state N-T by way of cAMP and decreasing P-o by unknown mechanisms. Despite appreciable PGE(2)-related decreases of P-o, the net stimulation of transport occurs by a considerably greater cAMP-mediated increase of N-T.