The modifying effects of amiloride on the thermosensitivity of Chinese hamster V-79 cells were examined under both neutral (pH 7.3) and acidic (pH 6.6) conditions. Amiloride, a diuretic drug, is known to inhibit the Na+/H+ exchange activity. Under the extracellular pH of 7.3, amiloride (0.1-0.5 mM) enhanced the thermal cell killing powers of 42 degrees C hyperthermia with increasing concentrati...

The effects of amiloride and a series of amiloride analogs have been tested on the Na(+)/H(+) antiport activity in intact vacuoles and tonoplast vesicles isolated from sugar beet cell suspension cultures. There is a competitive interaction between amiloride analogs and sodium. Substitution of one or both H-atoms of the 5-amino group of amiloride (apparent K(i) about 150 micromolar) resulted in ...

The electrochemical defect in the bronchial epithelium in cystic fibrosis (CF) consists of defective chloride secretion and excessive sodium reabsorption. The sodium channel blocker, amiloride, has been shown to reversibly correct the sodium reabsorption in CF subjects, but long term studies of amiloride have been disappointing due to its short duration of action. Benzamil, a benzyl substituted...

Inhaled amiloride has been recently demonstrated to have an effect on the decline of pulmonary function in patients with cystic fibrosis. Other diuretics have been demonstrated to provide protection against bronchoconstriction in asthmatic subjects. We report on the effect of inhaled amiloride on cold air hyperventilation challenge (CAHC) and methacholine challenge in asthmatics. We studied nin...

A known side-activity of the oral potassium-sparing diuretic drug amiloride is inhibition of the enzyme urokinase-type plasminogen activator (uPA, K(i)=7 μM), a promising anticancer target. Several studies have demonstrated significant antitumor/metastasis properties for amiloride in animal cancer models and it would appear that these arise, at least in part, through inhibition of uPA. Selectiv...

The activity of the NhaA Na+/H+ antiporter of Vibrio parahaemolyticus is inhibited by amiloride. We found an amino acid sequence in the NhaA that was identical to a putative amiloride binding domain of the Na+/H+ exchanger in mammalian cells. We constructed mutant NhaAs that had amino acid substitutions in the putative amiloride binding domain by site-directed mutagenesis. These include V62L (V...

Inhibition of the sodium-proton exchanger (NHE) plays an important role in reducing tissue damage during ischemic reperfusion injury; however, pharmacological inhibitors of NHE have restricted access to acutely ischemic tissues because of severely compromised tissue perfusion. We describe the syntheses, characterization, and NHE inhibitory activities of a novel class of amiloride derivatives wh...

Amiloride, an inhibitor of Na+/H+ exchange, was added at various concentrations to the culture medium of rabbit mammary explants. In the concentration range 100-250 microM, amiloride progessively inhibited 14C-thymidine incorporation induced by insulin, EGF or prolactin. Up to 250 microM, amiloride, which did not inhibit basal protein synthesis, was not cytotoxic, but it reduced basal DNA synth...

Split gill lamellae and gill cuticles of shore crabs (Carcinus maenas) adapted to 10 per thousand salinity were mounted in a modified Ussing-type chamber. With NaCl saline on both sides, split gill lamellae generated a short-circuit current (I(sc)) of -301+/-16 microA cm(-2) at a conductance (G(te)) of 40+/-2 mS cm(-2). The net influxes of Na(+) and Cl(-) were 8.3+/-2.6 and 18.2+/-2.7 micromol ...

In a two-bottle test, Sprague-Dawley rats preferentially consume a greater amount of hypotonic and isotonic NaCl solutions relative to water, whereas inbred Fischer 344 (F344) rats fail to prefer NaCl solutions at any concentration relative to water. To determine whether taste contributes to this strain difference, we measured the integrated neural responses of the chorda tympani nerve to a con...