A B S T R A C T Vasopressin increases the permeability of the totad urinary bladder, an analogue of the mammalian renal collecting duct, to water and small solutes, especially the amide urea. We have observed that three general anesthetic agents of clinical importance, the gases methoxyflurane and halothane and the ultrashortacting barbiturate methohexital, reversibly inhibit vasopressin-stimulated water flow, but do not depress permeability to urea, or to the lipophilic solute diphenylhydantoin.In contrast to their effects in vasopressin-treated bladders, the anesthetics do not inhibit cyclic AMP-stimulated water flow, consistent with an effect on vasopressin-responsive adenylate cyclase. The selectivity of the anesthetic-induced depression of water flow suggests that separate adenylate cyclases and cyclic AMP pools may exist for control of water and urea permeabilities in the toad bladder. Furthermore, theophylline's usual stimulatory effect on water flow, but not its effect on urea permeability, was entirely abolished in methoxyfluranetreated bladders, suggesting that separate phosphodiesterases that control water and urea permeabilities are present as well.We would conclude that the majority of water and urea transport takes place via separate pathways across the rate-limiting luminal membrane of the bladder cell, and that separate vasopressin-responsive cellular pools of cyclic AMP appear to control permeability to water and to urea.
INTRODUCTIONThere is evidence in several epithelial tissues that water and small amides such as urea cross the cell membrane via independent pathways. In the toad urinary bladder, for example, vasopressin-stimulated urea transport is blocked by agents such as phloretin, tannic acid, and the oxidizing agents permanganate and chromate, while osmotic water flow is unaltered (1-3). These inhibitory agents appear to act at a luminal membrane site, beyond the generation of cyclic AMP, since cyclic AMPstimulated urea transport is inhibited as effectively as transport stimulated by vasopressin (3).The present study describes the action of three anesthetic agents, the gases methoxyflurane and halothane and the short-acting barbiturate methohexital, which have an effect opposite to that of phloretin and the oxidizing agents; the inhibition of osmotic water flow with no alteration in urea transport. In contrast to the selective inhibitors of urea transport, the anesthetics do not inhibit cyclic AMP-stimulated water movement. This suggests that the independent pathway for xvater movement may involve not only a separate site for penetration at the luminal membrane, but a specific and separate adenylate cyclase-cyclic AMP-mediated control system as well.