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)

TPA (12-O-tetradecanoylphorbol-13-acetate) is an effective tumor promoter that affects a variety of ion transport processes. To examine the relationship between effects on transport and growth and differentiation, we have been studying the actions of TPA on frog skin, a particularly well-characterized epithelium. We have reported that high concentrations of TPA stimulate base-line short-circuit current (ISC) and inhibit the subsequent natriferic action of vasopressin. The current study of 89 preparations extends those findings. The Km of the stimulatory effect of TPA is approximately 3 nM; this high affinity indicates that the transport phenomenon does not simply reflect a nonspecific interaction of phorbol ester with the plasma membranes. TPA acts largely or entirely at the mucosal surface of both split and whole skins; thus the sidedness of the effect does not arise from adsorption onto the underlying connective tissue when TPA is applied to the serosal surface of whole skin. Amiloride, an inhibitor of apical Na+ entry, abolishes ISC across frog skins pretreated with TPA. The phorbol ester also increases ISC across split skins, preparations which do not produce net Cl-transport. Indomethacin (1 microM) blocks PGE1 release, but does not alter the response to TPA at a fivefold lower concentration than previously used. NDGA (nordihydroguaretic acid, 10 microM), an inhibitor of the lipoxygenase pathway, partially inhibited the responses of ISC to 8 nM TPA. The present results indicate that frog skin is highly responsive to TPA at concentrations known to activate protein kinase C in broken-cell preparations.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of TPA on short-circuit current across frog skin. 310 64

We examined the electrophysiological and Na+ transport characteristics of rat papillary collecting duct (PCD) cells grown in primary cultures. Grown as monolayers on polycarbonate filters, the cells displayed similar morphological characteristics to native epithelia. They also bound Dolichus biflorus lectin, a property shared by native cells. Monolayers developed a peak electrical resistance of 100-200 omega.cm2 and a transmonolayer voltage of less than 2 mV. Similar values were measured in the perfused, native PCD of the same species as well as PCD cells cultured from rabbit and bovine kidneys. Hamster cells did not readily develop confluent monolayers under the same conditions. Exposure of the cultured cells to 10% fetal calf serum for 24 h caused the Na+ uptake across the apical membrane to double, an effect not reproduced by indomethacin, insulin, vasopressin, aldosterone, dexamethasone, or hexamethylene bisacetamide (an inducer of differentiation). Amiloride (1 mM) inhibited Na+ uptake by 50-80%. The measured short-circuit current did not correlate with Na+ uptake and was clearly dissociated by exposure to serum. The results suggest that there is more than one mechanism of ion transport by the rat PCD.
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PMID:Characteristics of papillary collecting duct cells in primary culture. 314 84

From the analysis of several studies published from 1979 to 1986 comprising 1,172 patients, we estimated that glomerular filtration rate (GFR) was normal in 85% of unselected patients on chronic lithium therapy. The remaining 15% of patients displayed only mild reduction in GFR, clustering at approximately 60 mL/min. Thus, the data available to date do not support earlier concerns that long-term lithium therapy could eventuate into renal insufficiency. The most prevalent renal effect of lithium is impairment of concentrating ability, which we estimated to be present in at least 54% of 1,105 unselected patients on chronic lithium therapy. This defect translated into overt polyuria in only 19% of unselected cases. A renal lesion confined to the collecting tubule has been described in humans who have taken lithium for short periods of time. This lesion may represent the collecting tubule's response to the intracellular accumulation of lithium, which interferes with cAMP formation and results in an early and probably reversible inhibition of antidiuretic hormone (ADH)-mediated water transport. However, long-term lithium therapy may induce a progressive and partly irreversible defect in concentrating ability. The potential risk for dehydration associated with lithium-induced polyuria, as well as the discomfort inherent to this side effect, deserves evaluation and consideration for therapeutic intervention. Amiloride has additional advantages over conventional treatment of nephrogenic diabetes insipidus using thiazide diuretics. The action of amiloride on ADH-mediated water transport seems specific in as much as it is capable of preventing the uptake of lithium in high resistance epithelia and thereby prevents the inhibitory effect of intracellular lithium on water transport. Unlike thiazides, amiloride has a weak natriuretic effect and is less likely to increase plasma lithium levels by causing volume contraction. In addition, amiloride, by conserving potassium, obviates the need for potassium supplementation that is usually required to prevent hypokalemia when thiazides are used to treat lithium-induced polyuria. Since amiloride may prevent chronic intracellular lithium accumulation in the collecting tubule, future studies should elucidate whether amiloride also has a role in preventing lithium-induced chronic tubulo-interstitial damage.
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PMID:Prevalence, pathogenesis, and treatment of renal dysfunction associated with chronic lithium therapy. 331 89

The passive (lumen-to-bath) K+ permeation (KK) of rabbit cortical collecting tubules was measured before and after inhibition of Na+ transport. Inhibition of the Na-K pump with ouabain reduced KK. This result contrasts sharply with the previously described increase in KK observed following inhibition of Na+ transport with amiloride. These opposite changes in KK are owing to the fact that a substantial component of the lumen-to-bath K+ permeation involves a transcellular pathway. Amiloride, because it hyperpolarizes the apical membrane, increases KK; ouabain, because it depolarizes the cell, decreases KK. Previous results have also suggested that the cell K+ permeability is secondarily altered by these agents so that the changes in voltage and permeability are additive. These patterns of changes in KK were used to evaluate the mechanism of action of two agents that partially inhibit Na+ transport: vasopressin and prostaglandin (PG) E2. Their effect on KK was qualitatively similar to that of amiloride. In amiloride-treated tubules, neither vasopressin nor PGE2 altered KK. Neither did they alter the normal reduction in KK caused by pump inhibition. Thus they did not have any direct effect on K+ permeability. These results are consistent with the thesis that vasopressin and PGE2 inhibit Na+ absorption by reducing apical membrane permeability. The relation between the regulation of Na+ absorption and K+ permeation may have important implications for the regulation of K+ secretion by the cortical collecting tubule.
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PMID:Patterns of K+ permeation following inhibition of Na+ transport in rabbit cortical collecting tubule. 345

The effects of amiloride and of natural aliphatic polyamines on basal and hormone-stimulated protein phosphorylations in hepatocytes were studied. Cells isolated from adult rats were incubated in suspension with (32P)-orthophosphate, in the absence or presence of the effectors at varying concentrations and for different times; hepatocytes were then exposed to various hormones for 10 min. Phosphoproteins contained in total cell lysates were analyzed by one- and two-dimensional gel electrophoresis and autoradiography. Amiloride and spermine (the most effective amine) decreased the basal level of phosphorylation of proteins of 46, 34 and 22 kDal, and increased that of 18 kDal and 93 kDal proteins. These effects were maximal with external concentrations of 1 mM and 7.5-10 mM amiloride and spermine, respectively. They were detectable after a lag period of about 10 min and reached a plateau after 45 min. Pretreatment of cells with these effectors almost completely prevented stimulation of the phosphorylation of the 46 and 34 kDal proteins by insulin. In contrast, the effects of vasopressin on the same proteins were only partly inhibited, whereas those of glucagon appeared largely unaffected. The major effect observed in intact cells (i.e., decreased phosphorylation) could be reproduced in a cell-free system where no kinase activity persisted. Amiloride or spermine added directly to cell extracts strongly accelerated the dephosphorylation of 46 kDal protein and also of the 61 kDal protein identified as pyruvate kinase. Furthermore, restoration of the activity of this enzyme occurred concomitantly with dephosphorylation of the 61 kDal protein, an observation supporting the notion that amiloride and spermine could activate a phosphoprotein phosphatase.
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PMID:Insulin regulation of protein phosphorylation in hepatocytes. Studies using two effectors: amiloride and natural aliphatic polyamines. 390 16

Vasopressin-resistant diabetes insipidus is a common side effect of the treatment of affective disorders with lithium. We studied the effect of amiloride on lithium-induced polyuria in nine such patients receiving maintenance lithium therapy who had a vasopressin-resistant defect in urinary concentrating ability. After a mean (+/- S.E.) of 24 +/- 6 days of amiloride administration, the urine volume fell (from 4.7 +/- 0.6 to 3.1 +/- 0.3 liters per 24 hours; P less than 0.005), and the urine osmolality increased (from 228 +/- 35 to 331 +/- 34 mOsm per kilogram of H2O; P less than 0.001). The decrease in urine output was sustained during six months of observation in the absence of any significant change in plasma levels of lithium, potassium, or bicarbonate; urinary excretion of sodium or lithium; or creatinine clearance. Amiloride administration was also associated with a significant increase in urine osmolality (from 575 +/- 54 to 699 +/- 48 mOsm per kilogram of H2O; P less than 0.005) measured after fluid deprivation and the injection of exogenous vasopressin. We conclude that amiloride mitigates lithium-induced polyuria, at least partly, by blunting the inhibitory effect of lithium on water transport in the renal collecting tubule. Thus, amiloride may provide a specific therapy for polyuria in lithium-treated patients while obviating the need for potassium supplementation in the treatment of this kind of polyuria.
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PMID:Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. 396 96

Amiloride in 10(-3) M concentration inhibits incompletely the short circuit current and active potential difference across the bovine corneal endothelium in vitro. The drug effect is reversible and unilateral, e.g. the drug is effective only from the aqueous side. The amiloride effect is compared to the effect of ouabain, nystatin and vasopressin on the same electrical parameters. The effect of these drugs support a model for active Na+ transport across the corneal endothelium with two separate pathways for Na+ transport - one for extrusion and one for reentry.
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PMID:Amiloride inhibition of Na+-entry into corneal endothelium. 401 90

1. Amiloride reduces short-circuit current and potential difference across the isolated frog skin.2. Isotopically measured sodium influx and efflux are diminished.3. Total electrical conductance and partial sodium conductance are diminished, the reduction in total conductance being entirely accounted for by the reduction in partial sodium conductance.4. The effect of antidiuretic hormone (ADH), cyclic 3'5'-adenosine monophosphate (cyclic AMP) and theophylline can be antagonized by pretreatment with amiloride but the antagonism can be abolished by increasing the concentration of these compounds.5. Amiloride has no effect on oxygen consumption in concentrations which inhibit sodium transport. However, it prevents the stimulatory effect of ADH on oxygen consumption.6. The results are consistent with an action of amiloride at the passive outside membrane of the transporting cells of isolated frog skin.
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PMID:Effects of amiloride on active sodium transport by the isolated frog skin: evidence concerning site of action. 431 93

1 Amiloride inhibits Na transport and short-circuit current (SCC) across the toad bladder. It is 1000 times more active at the mucosal than serosal surface. The lowest effective concentration was 10(-7)M.2. The inhibition was non-competitive with the sodium on the mucosal side of the bladder.3. Vasopressin, cyclic adenosine monophosphate (AMP) and aldosterone increased Na transport and SCC across the bladder and these effects were inhibited by amiloride.4. The antagonism of amiloride for vasopressin was non-competitive.5. Amphotericin B also increases Na transport across the bladder but its action was not changed by amiloride.6. Amiloride was without effects on SCC and diffusion potentials in bladders metabolically inhibited with CN(-) and iodoacetic acid (IAA).7. Neither plasma albumin, Ca(2+) nor adenosine triphosphate (ATP) altered the effects of amiloride.8. The only structural analogue of amiloride found to reduce SCC similarly was guanidine which was 1000 times less active. Pyrazine and a substituted pyrazine analogue were without effect. Neither guanidine nor the substituted pyrazine compound were competitive with amiloride.9. Amiloride had no effect on the osmotic permeability of the toad bladder either in the presence or absence of vasopressin.10. Na transport across the toad colon was also reduced by 10(-5)M amiloride at the mucosal surface.11. The possible mechanism of action of amiloride is discussed.
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PMID:Amiloride: a potent inhibitor of sodium transport across the toad bladder. 564 23

Vasopressin enhanced the absorption of Na+ and Cl- across the short-circuited colon descendens from normal rats. This effect of vasopressin results from an increase in the mucosal to serosal movement of Na+ and Cl- and a decrease in the serosal to mucosal movement of Cl- and was accompanied with a decrease in the short-circuit current (ISC). Neither the base-line absorption of Na+ and Cl-, the vasopressin-induced increase in Na+ and Cl- absorption nor the decrease in ISC were inhibited by amiloride in the colon from normal rats. Colon descendens from rats treated for 3 days with dexamethasone had remarkably higher transmural potential difference (p.d.), tissue conductance (Gt) and ISC. The absorption of Na+ across the short-circuited colon descendens from dexamethasone-treated rats was increased 3-fold when compared to colon from normal rats. The absorption of Cl- in normal rats was reversed to Cl- secretion in treated rats. Amiloride rapidly and reversibly decreased the p.d., Gt and ISC in colon from dexamethasone-treated rats. The transport of Na+ was nearly completely inhibited by amiloride in treated rats. In contrast to its enhancing effects on Na+ absorption in colon from normal rats vasopressin did not enhance Na+ absorption in colon from dexamethasone-treated rats. This enhancement of Cl- absorption by vasopressin was retained in colon from treated rats. This enhancement of Cl- transport was due solely to a decrease in the serosal to mucosal movement of Cl- and was accompanied with a decrease in ISC and Gt. The results support the hypothesis that vasopressin causes inhibition of the electrogenic secretion of Cl- in colon from dexamethasone-treated rats. Furthermore, the results suggest that the increase in the mucosal to serosal movement of Na+ and Cl- and the decrease in the serosal to mucosal movement of Cl- in colon from normal rats are caused by independent effects of vasopressin.
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PMID:Effects of vasopressin on electrolyte transport across isolated colon from normal and dexamethasone-treated rats. 649 90


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