Actions of isoproterenol in frog proximal tubules

In the present work, we compared biochemical and electrophysiological actions of isoproterenol on frog proximal tubular cells by using tubule suspensions and giant entities obtained by cell fusion. Isoproterenol (ISO) dose-dependently stimulated cAMP production in tubule suspension and depolarized the "giant cell" membrane. Both effects were triggered by beta receptor occupancy, but strongly differed in their concentration-dependency, since depolarization occurred with an ISO concentration as low as 10(-12) mol/l whereas cAMP accumulation could be seen only with more than 10(-8) mol/l ISO. ISO-induced membrane depolarization was mimicked by forskolin which directly stimulated the catalytic subunit of adenylyl cyclase. In both isoproterenol- and forskolin-stimulated giant cells, membrane depolarization was accompanied by a decrease in membrane conductance, and both effects were inhibited by tetraethylammonium (TEA) and 4-aminopyridine (4-AP). On the other hand, ISO- and forskolin-induced cAMP production were not affected by TEA. The present data thus show that isoproterenol produces two independent effects in frog proximal tubule: it depolarizes the cell membrane by blocking a K+ conductance and activates adenylyl cyclase.