Effect of metabolic inhibitors on vasopressin-stimulated transport systems in the toad bladder.
Vasopressin increases the permeability of receptor cells to water and, in tissues such as toad bladder, to solutes such as urea. While cyclic AMP appears to play a major role in mediating the effects of vasopressin, there is evidence that activation of the water permeability system and the urea permeability system involves separate pathways. In the present study, we have shown that inhibitors of oxidative metabolism (rotenone, dinitrophenol, and methylene blue) selectively inhibit either vasopressin-stimulated water flow or vasopressin-stimulated urea transport. There was no inhibition, however, when exogenous cyclic AMP was substituted for vasopressin, and little to no inhibition when the potent analogue 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) was employed. Rotenone had no effect on adenylate cyclase activity or cyclic AMP levels within the cell; dinitrophenol decreased adenylate cyclase activity minimally. Additional studies with vinblastine and nocodazole, inhibitors of microtubule assembly, demonstrated an inhibition of vasopressin and cyclic AMP-stimulated water flow but showed no effect on urea transport. We would conclude that water and urea transport, as examples of hormone-stimulated processes, have different links to cell metabolism, and that in addition to cyclic AMP, a non-nucleotide pathway may be involved in the action of vasopressin.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002024:Bufo marinus; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D012402:Rotenone / Q000494:pharmacology; D014508:Urea / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology*
D004140:Dinitrophenols; D012402:Rotenone; D014667:Vasopressins; D014508:Urea; D000242:Cyclic AMP; D000262:Adenylyl Cyclases