DUAL ROLE OF PROSTAGLANDINS (PGE(2)) IN REGULATION OF CHANNEL DENSITYAND OPEN PROBABILITY OF EPITHELIAL NA-SKIN (R-PIPIENS)( CHANNELS IN FROG)

Prostaglandins are important in signaling pathways involved in modulat ing the rates of Na+ transport in a diverse group of tissues possessin g apical membrane epithelial channels. PGE(2) is known to cause either stimulation, inhibition or transient stimulatory changes of Na+ trans port. We have continued our studies of frog skins that are known to re spond to forskolin and PGE(2) with large steady-state increases of tra nsport and have used noninvasive methods of blocker-induced noise anal ysis of Na+ channels to determine their channel densities (N-T) and op en probabilities (P-o). In the absence of exogenous hormones, baseline rates of Na+ transport are especially high in scraped skins (R. pipie ns pipiens) studied in the fall season of the year. Na+ transport was inhibited by indomethacin and by removal of the unstirred layers of th e cerium (isolated epithelia) alone suggesting that PGE(2) is responsi ble for the sustained and elevated rates of transport in scraped skins . Changes of transport caused by indomethacin, forskolin or PGE(2) wer e unquestionably mediated by considerably larger changes of N, than co mpensatory changes of P-o. Since cAMP caused no change of P, in tissue s 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 decre asing P-o by unknown mechanisms. Despite appreciable PGE(2)-related de creases of P-o, the net stimulation of transport occurs by a considera bly greater cAMP-mediated increase of N-T.