The effect of val5-angiotensin II on steady-state sodium concentration gradients (deltacNa) was studied in rat proximal tubules by stationary micro-perfusion combined with perfusion of the peritubular capillaries. Angiotensin added to the peritubular perfusion fluid had a biphasic action with stimulation of sodium reabsorption at low doses (10(-12)-10(-10)M) and inhibition at high doses (3 X 10(-7) - 3 X 10(-6)M). Stimulation of transport was also observed with intraluminal angiotensin but only at a dose of 10(-9)M. Transepithelial potential difference was calculated from the steady-state chloride distribution; no significant change was observed at low (10(-11)M) or high (10(-6)M) concentrations and a direct action on sodium transport is postulated. This biphasic effect is discussed in relation to the responses of the intact kidney to intra-renal infusion of angiotensin, and to the control of tubulo-glomerular feed-back.

No abstract

Many pathogens causing diarrhea do so by modulating ion transport in the gut. Respiratory pathogens are similarly associated with disturbances of fluid balance in the respiratory tract, although it is not known whether they too act by altering epithelial ion transport. Here we show that influenza virus A͞PR͞8͞34 inhibits the amiloride-sensitive Na ؉ current across mouse tracheal epithelium with a half-time of about 60 min. We further show that the inhibitory effect of the influenza virus is caused by the binding of viral hemagglutinin to a cell-surface receptor, which then activates phospholipase C and protein kinase C. Given the importance of epithelial Na ؉ channels in controlling the amount of fluid in the respiratory tract, we suggest that down-regulation of Na ؉ channels induced by influenza virus may play a role in the fluid transport abnormalities that are associated with influenza infections.hemagglutinin ͉ protein kinase C ͉ ENaC ͉ phospholipase C

No abstract

Our previously published whole-cell patch-clamp studies on the cells of the intralobular (granular) ducts of the mandibular glands of male mice revealed the presence of an amiloride-sensitive Na+ conductance in the plasma membrane. In this study we demonstrate the presence also of a Cl- conductance and we show that the sizes of both conductances vary with the Cl- concentration of the fluid bathing the cytosolic surface of the plasma membrane. As the cytosolic Cl- concentration rises from 5 to 150 mmol/liter, the size of the inward Na+ current declines, the decline being half-maximal when the Cl- concentration is approximately 50 mmol/liter. In contrast, as cytosolic Cl- concentration increases, the inward Cl- current remains at a constant low level until the Cl- concentration exceeds 80 mmol/liter, when it begins to increase. Studies in which Cl- in the pipette solution was replaced by other anions indicate that the Na+ current is suppressed by intracellular Br-, Cl- and NO3- but not by intracellular I-, glutamate or gluconate. Our studies also show that the Cl- conductance allows passage of Cl- and Br- equally well, I- less well, and NO3-, glutamate and gluconate poorly, if at all. The findings with NO3- are of particular interest because they show that suppression of the Na+ current by a high intracellular concentration of a particular anion does not depend on actual passage of that anion through the Cl- conductance. In mouse granular duct cells there is, thus, a reciprocal regulation of Na+ and Cl- conductances by the cytosolic Cl- concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Epithelial Na ؉ channels are expressed widely in absorptive epithelia such as the renal collecting duct and the colon and play a critical role in f luid and electrolyte homeostasis. Recent studies have shown that these channels interact via PY motifs in the C terminals of their ␣, ␤, and ␥ subunits with the WW domains of the ubiquitin-protein ligase Nedd4. Mutation or deletion of these PY motifs (as occurs, for example, in the heritable form of hypertension known as Liddle's syndrome) leads to increased Na ؉ channel activity. Thus, binding of Nedd4 by the PY motifs would appear to be part of a physiological control system for down-regulation of Na ؉ channel activity. The nature of this control system is, however, unknown. In the present paper, we show that Nedd4 mediates the ubiquitin-dependent down-regulation of Na ؉ channel activity in response to increased intracellular Na ؉ . We further show that Nedd4 operates downstream of G o in this feedback pathway. We find, however, that Nedd4 is not involved in the feedback control of Na ؉ channels by intracellular anions. Finally, we show that Nedd4 has no inf luence on Na ؉ channel activity when the Na ؉ and anion feedback systems are inactive. We conclude that Nedd4 normally mediates feedback control of epithelial Na ؉ channels by intracellular Na ؉ , and we suggest that the increased Na ؉ channel activity observed in Liddle's syndrome is attributable to the loss of this regulatory feedback system.

No abstract

SUMMARY1. HCO-, Na+ and K+ concentrations were measured in bile-free pancreatic juice collected from fasted and fed anaesthetized rats.2. Resting flow rates averaged 0-62 sal. g'1. min-' (fasted) and 2-8 /11. mi1 (fed) and the mean HCO-j concentainrseivlwe 25-8 and 33-3 mm. 3. In fasted rats, instillation of HC1 into the duodenum caused flow rate to increase threefold and HCO3 concentrations to double (66 mm).