Membrane pathways for water and solutes in the toad bladder: I. Independent activation of water and urea transport

Abstract

Vsopressin activates a number of transport systems in the toad bladder, including the systems for water, urea, sodium, and other small solutes. Evidence from experiments with selective inhibitors indicates that these transport systems are to a large extent functionally independent. In the present study, we show that the transport systems can be separately activated. Low concentrations of vasopressin (1 mU/ml) activate urea transport with virtually no effect on water transport. This selective effect is due in part to the relatively greater inhibitor action of endogenous prostaglandins on water transport. Low concentrations of 8-bromoadenosine cyclic AMP, on the other hand, activate water, but not urea transport. In additional experiments, we found that varying the ratio of exogenous cyclic AMP to theophylline activated water or urea transport selectively. These studies support the concept of independently controlled systems for water and solute transport, and provide a basis for the study of individual luminal membrane pathways for water and solutes in the accompanying paper.

Interaction of vasopressin and prostaglandins in the toad urinary bladder.

“…There is strong evidence that this response can be influenced by prostaglandins. Specifically, administration of exogenous prostaglandin (PG)E, or E, can markedly inhibit the response of the toad bladder (2)(3)(4) and isolated collecting tubule (5) to AVP. Inhibition of endogenous prostaglandin synthesis by cyclo-oxygenase inhibitors, on the other hand, enhances the response to AVP, both in vitro in toad bladder (3) and in vivo in animals (6,7) and man (6).…”

Role of the endogenous kallikrein-kinin system in modulating vasopressin-stimulated water flow and urea permeability in the toad urinary bladder.

“…Thus, inhibition of kinin production by aprotinin reduced vasopressin's effect to increase urea permeability, whereas augmenting kinin production with captopril potentiated the increase in urea permeability stimulated by vasopressin. Previous studies have provided evidence for the concept that the pathways mediating water and urea transport are to a significant extent independent and distinct from one another (3,16,17). This concept is strengthened by the original observation ofthis study that endogenous kinins modulate vasopressin's action on the water and urea transport pathways in opposite directions.…”

“…The action of vasopressin on transepithelial water transport has been shown to be modulated by several hormonal systems including aldosterone (1) and prostaglandins (2,3). Several lines of indirect evidence suggest that the kallikrein-kinin system may also modulate the action of vasopressin.…”

“…The results demonstrate that inhibition of the endogenous kallikrein-kinin system augments vasopressin-stimulated water flow but depresses vasopressin-stimulated urea transport, whereas activation of the endogenous kallikrein-kinin system depresses vasopressin-stimulated water transport but augments vasopressin-stimulated urea permeability. The opposite effects of the kallikrein-kinin system on vasopressinstimulated water and urea transport makes this endogenous modulator system distinct from aldosterone and prostaglandins, both of which alter water and urea transport in the same direction (1,3). METHODS Female Dominican toads (National Reagents, Bridgeport, Conn.) were doubly pithed, and glass bongs were tied into both hemibladders in situ.…”

Inhibition of Urea Tubular Reabsorption by PGE₁ Infusion in Man

“…Inhibitors o f water flow decreased the number o f aggregates, i.e., vasopressin-in duced intramembranous particles, while an inhibitor of urea transport had no effect on aggregate size or number [12], indicating that the particle aggregates mediate water but not solute transport. Furthermore, other studies indi cate that PG independently stimulate the transport o f water and urea in the toad bladder [13,14], Therefore, no data are available in the clinical and experimental literature allowing a definition o f the interac tion between PG given by systemic infusion and renal urea handling and of the intrarenal mechanism(s) responsible for the reduced reabsorption o f this solute. The aim of the present study is to evaluate if: (1) PG affect the tubular transport of urea in man by counteracting the hydrosmotic effects of ADH and, hence, by decreasing passive reabsorp tion o f urea, or (2) PG have an action on epithelial tubular transport of urea, independent o f its interaction with ADH.…”