Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reversible inhibition of transepithelial sodium transport achieved with amiloride (and triamterene) was evaluated in amphibian preparations stimulated with aldosterone so as to provide further information regarding a possible influence of this hormone on the apical border of target cells. When aldosterone secretion was enhanced by withdrawal of sodium from toad (Bufo marinus) habitat, sensitivity of abdominal skin to amiloride decreased; the same occurred in skin and bladder preparations incubated with aldosterone for several hours. Amiloride proved a less efficient blocker of sodium transport by toad skin exposed to vasopressin and to ouabain; both substances are capable or raising cell sodium content. It is therefore proposed that the decrease in sensitivity to amiloride of amphibian epithelial treated with aldosterone results from an increase in target cell sodium, itself due to a hormone-induced increas in sodium conductance at the apical cell border. Glucose, which enhanced markedly the rate of sodium transport in preparations treated with aldosterone for several hours, failed to decrease any further the response to amiloride; this is taken as an argument for an additional (? secondary) influence of aldosterone on the cell's metabolic machinery connected with the operation of the sodium 'pump'.
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PMID:Decreased sensitivity to amiloride of amphibian epithelia treated with aldosterone. Further evidence for an apical hormonal effect. 677 Mar 38

Addition of Na+ to Na+-depleted Swiss 3T3 cells causes a rapid and dramatic increase in intracellular pH, as monitored by uptake of the weak acid 5,5-dimethyloxazolidine-2,4-dione. The effect of Na+ is concentration dependent (half-maximal effect at 38 mM); this cation can be replaced by Li+ but not by K+ or the choline ion. Amiloride prevents the Na+-induced increase in intracellular pH and also blocks the entry of Na+ into 3T3 cells; the half-maximal concentrations of amiloride for inhibiting the two processes are similar (40 microM). Increase in extracellular pH caused an increase in the initial rate of Na+ influx that was of sufficient magnitude to stimulate the activity of the Na+/K+ pump in quiescent 3T3 cells. Taken together, these findings suggest the presence of a functional Na+/H+ antiport in Swiss 3T3 cells. Addition of the potent mitogenic combination platelet-derived growth factor, vasopressin, and insulin to quiescent Swiss 3T3 cells increased the intracellular pH from 7.21 +/- 0.07 to 7.36 +/- 0.09 in 10 independent experiments (P less than 0.001). This combination of growth factors also stimulated Na+ entry and ouabain-sensitive Rb+ uptake. The data support the hypothesis that early changes in ion fluxes play a role in signaling mitogenesis in 3T3 cells.
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PMID:Na+/H+ antiport in Swiss 3T3 cells: mitogenic stimulation leads to cytoplasmic alkalinization. 696 50

Sour taste perception depends primarily on the concentration of H+ in the taste stimulus. Acid stimuli elicit concentration-dependent action potentials in taste cells. Recent patch-clamp studies suggest that protons depolarize taste cells by direct interaction with apically located ion channels. In Necturus maculosus, the voltage-dependent K+ conductance is restricted to the apical membrane of taste cells. The current flows through a variety of K+ channels with unitary conductances ranging from 30 to 175 pS, all of which are blocked directly by citric acid applied to outside-out or perfused cell-attached patches. In contrast, hamster fungiform taste cells appear to utilize the amiloride-sensitive Na+ channel for acid transduction. Amiloride completely inhibits H+ currents elicited by acid stimuli in isolated taste cells, with an inhibition constant similar to that for amiloride-sensitive Na+ currents (Ki = 0.2 microM). Treatment of isolated taste cells with the bioactive peptide arginine-vasopressin results in similar increases in both the amiloride-sensitive Na+ and H+ currents; the effect is mimicked by 8-bromocyclic AMP. These results suggest that H+ can permeate amiloride-sensitive Na+ channels in hamster fungiform taste cells, contributing to the transduction of sour stimuli.
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PMID:Role of apical ion channels in sour taste transduction. 751 71

Urea is transported from mucosa to serosa across the skin of the stenohaline toad, Bufo marinus, studied under short circuit current (SCC) conditions. Mucosal to serosal transepithelial urea transport (Jm-->s(urea)) was markedly and asymmetrically enhanced in toads adapted to hypertonic (150 mM) NaCl and showed saturation kinetics with an estimated Kd for urea in the bathing solution of approximately 1 mM and a maximal rate of Jm-->s(urea) = 9.4 nmol.cm-2 x hr-1, consistent with a carrier-mediated transport mechanism. Jm-->s(urea) in the skin of 150 mM NaCl-adapted toads was characterized with drugs known to affect transepithelial urea transport (J(urea)) in the urinary bladder of this species. Amiloride (10(-8)-10(-3) M) inhibited Jm-->s(urea) in a dose-dependent fashion, but with a potency only 1/1000th of that for inhibition of SCC in the same skins. Phloretin (< or = 5 x 10(-4) M) had no effect on Jm-->s(urea) or SCC; ouabain (5 x 10(-4) M) and NaCN (10(-3) M) had no effect on Jm-->s(urea) but inhibited SCC (indicating inhibition of active sodium transport) by 70 and 67%, respectively and vasopressin (10(-8) M) had no effect on Jm-->s(urea), but stimulated SCC 179% above base line. The pyrazinoyl amiloride analog, 2-pyrazinoylguanidine (10(-4) M), reported to inhibit urea transport in mammals, also had no effect on Jm-->s(urea), but inhibited SCC approximately 30%. A 1.5 unit pH gradient (m-->s or s-->m) had no effect on Jm-->s(urea).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Urea transport in toad skin (Bufo marinus) 822 63

Amiloride has been suggested to inhibit responses to a variety of taste stimuli, including salty, sweet, and sour (acid). To test for the involvement of amiloride-sensitive Na+ channels in the transduction of acid stimuli, fungiform taste receptor cells were examined using patch-clamp techniques. Approximately one-half of all cells had amiloride-sensitive Na+ currents (INa) with a Ki value near 0.2 microM amiloride. After blocking voltage-gated conductances, cells having amiloride sensitivity were tested for responses to acid stimuli. Over three-fourths of cells showed an inward proton current (IH+) with an extrapolated reversal potential near approximately +150 mV, which was completely blocked by amiloride (30 microM). Treatment of isolated taste cells with arginine8-vasopressin caused equivalent increases in both INa and IH+; each effect was mimicked by 8-Br-cAMP. Taken together, these results indicate that protons permeate amiloride-sensitive Na+ channels in hamster fungiform taste cells and contribute to acid transduction.
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PMID:Proton currents through amiloride-sensitive Na+ channels in isolated hamster taste cells: enhancement by vasopressin and cAMP. 838 26

This study was undertaken to analyze whether the mechanism of decreased fractional lithium excretion (FELi) induced in humans by the prostaglandin synthesis inhibitor indomethacin and the vasopressin analog desamino-8-D-arginine vasopressin (d-DAVP) is amiloride inhibitable. Eight sodium-restricted (10 mmol/day) healthy volunteers underwent clearance studies to evaluate the effects of indomethacin (50 mg tid for 6 days), amiloride (10 mg twice before the clearance study) and d-DAVP (4 micrograms, i.v.), and combinations of these drugs. Despite the sodium restriction, amiloride had no effect on FELi, although the dosage was sufficient to cause a 6-fold increase in sodium excretion, and potassium retention. Compared to a base-line value of 27.9 +/- 2.1%, FELi fell to 20.7 +/- 2.1% after indomethacin (P < .01) and to 22.4 +/- 1.5% after d-DAVP (P < .01). When d-DAVP was administered during indomethacin, the FELi fell to 18.0 +/- 1.4%. Compared to indomethacin alone, this represented no significant further change. Amiloride did not prevent the fall in FELi caused by indomethacin or d-DAVP or both. These data indicate that in humans, 1) sodium restriction does not cause amiloride-sensitive lithium reabsorption, and 2) the lithium reabsorption caused by d-DAVP and indomethacin is not amiloride sensitive.
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PMID:Indomethacin- and desamino-8-D-arginine vasopressin-induced lithium reabsorption is not amiloride sensitive in humans. 851 7

Lithium therapy frequently induces nephrogenic diabetes insipidus; amiloride appears to prevent its occurrence in some clinical cases. Amiloride blocks the epithelial sodium channel (ENaC) located in the apical membrane of principal cells; hence one possibility is that ENaC is the main entry site for lithium and the beneficial effect of amiloride may be through inhibiting lithium entry. Using a mouse collecting duct cell line, we found that vasopressin caused an increase in Aquaporin 2 (AQP2) expression which was reduced by clinically relevant lithium concentrations similar to what is seen with in vivo models of this disease. Further amiloride or benzamil administration prevented this lithium-induced downregulation of AQP2. Amiloride reduced transcellular lithium transport, intracellular lithium concentration, and lithium-induced inactivation of glycogen synthase kinase 3beta. Treatment of rats with lithium downregulated AQP2 expression, reduced the principal-to-intercalated cell ratio, and caused polyuria, while simultaneous administration of amiloride attenuated all these changes. These results show that ENaC is the major entry site for lithium in principal cells both in vitro and in vivo. Blocking lithium entry with amiloride attenuates lithium-induced diabetes insipidus, thus providing a rationale for its use in treating this disorder.
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PMID:Amiloride blocks lithium entry through the sodium channel thereby attenuating the resultant nephrogenic diabetes insipidus. 1936 30


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