Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The alpha-adrenergic agonist oxymetazoline increased Na+,K(+)-ATPase activity of single proximal convoluted tubules dissected from rat kidney. Activation of the enzyme by oxymetazoline was prevented by either the alpha 1-adrenergic antagonist prazosin or the alpha 2-adrenergic antagonist yohimbine and was mimicked by the calcium ionophore A23187. The effect of oxymetazoline on Na+,K(+)-ATPase activity was prevented by a specific peptide inhibitor of calcineurin, as well as by FK 506, an immunosuppressant agent known to inhibit calcineurin; these results indicate that the action of oxymetazoline is mediated via activation of calcineurin (a calcium/calmodulin-dependent protein phosphatase). Activation of the Na+,K(+)-ATPase by either oxymetazoline or A23187 was associated with a greater than 2-fold increase in its affinity for Na+. The results provide a biochemical mechanism by which norepinephrine, released from renal nerve terminals, stimulates Na+ retention.
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PMID:Calcineurin mediates alpha-adrenergic stimulation of Na+,K(+)-ATPase activity in renal tubule cells. 138 Jan 57

Chick embryos rendered calcium (Ca) deficient by shell-less (SL) culture develop hypertension and tachycardia. Since hypocalcemia is accompanied by hypernatremia systemically but not by lower cellular Ca (Koide and Tuan, 1989), we speculate that cellular Ca handling may be altered in the SL embryo, perhaps involving Na transport. Using erythrocytes (RBC) from day-14 SL and normal (NL) embryos as the experimental cell, cellular Ca handling was studied under varying extracellular osmotic and ionic conditions by analyzing 45Ca uptake and cell volume regulation. Two agents, p-chloromercuriphenylsulfonate (PCM), and inosine/iodoacetamide (INI) were used to treat the RBCs to modify plasma membrane ion permeability and to deplete cellular ATP, respectively. Other cellular functions and activities related to Ca homeostasis, including ATP content and Ca(2+)-ATPase activity, were also analyzed. These analyses showed: (1) in NaCl, Ca uptake was similar in NL and SL cells, except after INI treatment, which resulted in slower Ca uptake by the SL cells, (2) in choline and sucrose, Ca uptake by SL RBCs was higher, (3) Ca uptake by RBCs of both embryos changed depending on the osmotic agent (Na < K < or = choline < sucrose), (4) Ca(2+)-ATPase activity was higher in SL RBC, although there was no change in the size or charge of the enzyme, and (5) in any osmotic agent, cellular Na was significantly lower, whereas cellular K was higher, in SL RBC. Based on these results, three features of RBC Ca handling were apparent: (1) Na-Ca exchange was functional and was more active in SL RBCs, (2) Ca uptake was dependent on the total ionic electrochemical gradient but not on bulk H2O movement, and (3) Ca pumping out capacity was directly correlated with Ca(2+)-ATPase activity. Elevated Ca uptake in sucrose-treated SL RBC is therefore indicative of its greater ion permeability. Taken together, these findings indicate that cellular Ca handling of the RBCs of SL chick embryos is characterized by a more active Na-Ca exchange system, greater ion permeability, and higher Ca pumping out capacity, thereby suggesting an up-regulated Ca handling function in the SL RBCs. The abnormal cellular Ca handling may be a direct result of the systemic Ca deficiency of the SL chick embryo and may be functionally related to its hypertension and tachycardia.
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PMID:Alterations in cellular calcium handling as a result of systemic calcium deficiency in the developing chick embryo: I. Erythrocytes. 144 22

Renal function differs in term infants from that in adults, with lower glomerular filtration rate (GFR) and reduced proximal tubular reabsorption of sodium (Na) and water: nevertheless, it is adequate for their needs. This is not true of very preterm infants in whom hyponatraemia is common. Animal studies have shown that Na+, K(+)-ATPase and the Na+/K+ exchanger are poorly expressed at birth with rapid postnatal rises. Cell receptors for hormones that influence tubular Na transport are less numerous in the premature infant than later in life: intracellular second messenger systems may also be immature. The low GFR is due to vasoconstriction and may be necessary to prevent water and electrolyte wasting due to tubular overload. The hyponatraemia of prematurity could, in principle, be due either to Na loss or water excess and can be prevented either by giving additional Na or by restricting water intake. Na supplementation causes relative volume expansion (VE), water restriction volume contraction (VC); this is demonstrated by the effect of the two approaches on weight gain and on the levels of vasoactive hormones in the blood. We argue that moderate VE is more physiological than VC, both in attempting to simulate intrauterine conditions and in consideration of the infant's nutritional needs. The much less common complication of hypernatraemia is usually due to abnormal water loss and should be prevented by increasing water intake appropriately. The above applies to well, preterm babies: sick preterm infants are much more variable in their Na and water requirements than well infants of comparable gestation and weight and each needs an individually tailored regimen based on frequent clinical assessment and laboratory measurement.
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PMID:Salt and the newborn kidney. 202 43

Cyclosporin immunosuppression is mediated by a calcium/sodium excess during G0 which inhibits further cell cycle progression. The consequences of cyclosporin on electrolyte content were measured in T-lymphocytes stimulated with concanavalin A. Cyclosporin caused an excessive accumulation of extracellular calcium for the first 4 h of lectin stimulation. The nonpermissive calcium content resulted from a reduction in the rate of calcium efflux from the cell. Because cyclosporin did not affect calcium translocation via ATPase but did permit excessive amounts of sodium to enter the resting cell we hypothesized that the calcium excess is caused by a shut-down of the Ca2+/Na+ antiport during the first hours of lectin stimulation. The subsequent normalization of calcium content is coincident with the onset of mRNA synthesis, which suggests development of compensatory mechanisms to alleviate the calcium burden. The G0 calcium excess did not affect other transductive events such as ligand recognition, phosphatidyl inositol metabolism, or adenylate cyclase activation. This study points to the causative mechanism of cyclosporin immunosuppression and emphasized the dynamic role of ions as modulators of normal cell proliferation.
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PMID:Cyclosporin immunosuppression mediated by calcium/sodium imbalance. 253 94

Based on a review of literature in various fields of research related to hypertension, we develop a new working hypothesis on the pathophysiology of genetically determined increases in blood pressure. According to our hypothesis, the primary defect is located in the kidneys. Renal alpha-adrenergic receptor density is increased in the early stages of the disease, before increases in blood pressure occur. Most renal alpha-adrenergic receptors are located in the proximal tubules and enhance Na+ reabsorption. A genetically determined increase of alpha 1- or alpha 2- or of both alpha-adrenergic receptor subtypes would impair Na+ excretion and, together with increased Na+ intake, would lead to positive Na+ balance. Subsequently, various mechanisms would be activated to restore a neutral Na+ balance, including the secretion of a natriuretic factor that inhibits Na+/K+-ATPase. Inhibition of Na+/K+-ATPase in extrarenal tissues would increase the intracellular concentration of Na+ and, via Na+/Ca2+ exchange, of Ca2+. Elevated intracellular Ca2+ would enhance vascular smooth muscle contractility and neuronal transmitter release, thereby leading to vasoconstriction and to increases in blood pressure. We thus hypothesize that hypertension is a homeostatic response designed to protect blood volume from a genetically determined renal alpha-adrenergic receptor-mediated increase in Na+ retention.
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PMID:Renal alpha-adrenergic receptor alterations: a cause of essential hypertension? 253 29

To evaluate the role of increased thick ascending limb Na+-K+-ATPase activity in rats undergoing hypertonic salt loading, the following groups of rats were studied: 1) control rats, 2) rats receiving an oral hypertonic Na load for 7 days, and 3) rats receiving the same oral Na load as in group 2 plus a daily injection of 10 mg/100 g of furosemide ip for 7 days. Salt loading (group 2) was associated with increased glomerular filtration rate (GFR) and hence an increased filtered load of sodium. Plasma aldosterone levels were markedly decreased. Na+-K+-ATPase was unchanged in the proximal tubule [convoluted (PC) and straight (PS)], increased in the thick ascending limb of Henle's loop [outer medullary (OMTAL) and cortical (CTAL)] and decreased in the distal nephron [distal convoluted tubule (DCT) and cortical collecting duct (CCD)]. The renal corticomedullary gradient of solutes was markedly increased in the salt-loaded group. Salt loading plus furosemide for 7 days (group 3) was associated with severe dehydration and hypernatremia. GFR as well as plasma aldosterone levels were unchanged compared with control. Na+-K+-ATPase was significantly increased in the proximal tubule (PC and PS), markedly decreased in the thick ascending limb of Henle's loop (OMTAL and CTAL), increased in the DCT and unchanged in the CCD. The increase in the corticomedullary gradient caused by salt loading per se was abolished by treatment of salt-loaded rats with furosemide. These results indicate that treatment with furosemide prevents the preservation of water balance and of normal body fluid tonicity in rats undergoing hypertonic Na loading.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of thick ascending limb Na+-K+-ATPase activity in salt-loaded rats by furosemide. 253 44

In the proximal tubules, fractional reabsorption remains essentially unchanged during variations in glomerular filtration rate (GFR). Glomerulotubular balance (GTB), defined as the linear relationship between proximal tubular reabsorption and GFR, is quantitatively the most important regulator of tubular reabsorption, which may be stopped by inhibiting Na, K-ATPase activity completely. However, ouabain in doses inhibiting 80% of the Na, K-ATPases, exerts no effect on proximal reabsorption of water, NaCl and NaHCO3. At constant plasma pH, the same relationship between filtered and reabsorbed bicarbonate is obtained whether bicarbonate reabsorption is altered by varying GFR or plasma concentration of bicarbonate. In contrast, a selective rise in plasma NaCl concentration at constant plasma pH (hypernatremia) reduces NaHCO3 reabsorption and fails to stimulate NaCl reabsorption. Other characteristics of proximal tubular reabsorption are that nonreabsorbable solutes, such as mannitol, inhibit water and NaCl reabsorption with little or no change in NaHCO3 reabsorption and renal oxygen consumption. Mannitol reduces the slope of the GTB curve for NaCl but not for NaHCO3. Hypertonic NaHCO3 exerts an osmotic effect on proximal water and NaCl reabsorption comparable to that of mannitol, whereas hypertonic NaCl is without osmotic effect. By reducing plasma pH (hypercapnia at high plasma bicarbonate concentration), the slope of the GTB curves for NaCl and NaHCO3 can be greatly increased. By raising plasma pH either by hypocapnia or bicarbonate loading, proximal reabsorption of NaHCO3 and NaCl is greatly depressed and remains almost unaltered during variations of GFR (abolished GTB). Similarly, carbonic anhydrase inhibitors, such as acetazolamide, reduce the reabsorption of NaCl and NaHCO3 in the same proportion as a rise in plasma pH, and abolish GTB. Examinations of proximal tubular oxygen consumption indicate that the energy requirement for NaHCO3 reabsorption is as expected for transcellular transport by Na, K-ATPases, whereas proximal NaCl reabsorption requires no additional energy. These data indicate that transcellular energy-requiring NaHCO3 reabsorption provides the main osmotic force across the tight junction for paracellular reabsorption of proximal tubular fluid containing NaCl and other solutes of low reflection coefficient. The main factors influencing GTB are the filtered load of bicarbonate, plasma pH and nonreabsorbable solutes in the proximal tubular fluid.
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PMID:Essentials of glomerulotubular balance. 267 97

1. The effect of diabetes on renal sodium retention was investigated. 2. The technique involved retrograde perfusion from the renal veins via the kidneys, and then through the renal arteries and dorsal aorta. 3. Sodium retention by diabetic rat kidney was 58% lower than that in the normal rats. 4. Ouabain (15 mM) in perfusate increased sodium retention by 30% in normal rat kidney as compared to a 54% increase in diabetic rat kidney. 5. Ethacrynic acid (1 mM) in perfusate resulted in a 42% reduction in sodium retention in the normal rat kidney as compared to a 43% decrease in the diabetic rat kidney. 6. Control of hyperglycemia in diabetic rats with insulin therapy resulted in sodium retention that is not significantly different from that of normal rats. 7. The results suggest that diabetes has no effect on the peritubular ouabain-sensitive Na--K-ATPase pump, or the luminal ethacrynic acid-sensitive Na-K counter transport pump. Furthermore, the data suggest a reversible effect of diabetes on sodium retention during insulin therapy.
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PMID:Effect of diabetes on natriuresis in the presence of ouabain and ethacrynic acid in perfused rat kidney. 288 71

Na-K-ATPase is an ubiquitous enzyme involved in the tubular reabsorption process. Na-K-ATPase is specifically controlled in each nephron segment. Sodium retention is one of the main features of the nephrotic syndrome. Hypervolemia is found in most of the nephrotic syndromes in adults, suggesting a primary renal origin. In the puromycin-induced nephrotic syndrome in rats, the collecting duct is the site of sodium retention. We have shown that Na-K-ATPase activity is specifically enhanced in collecting ducts from rats with puromycin-induced nephrotic syndrome. The stimulation of Na-K-ATPase activity was independent of aldosterone and endogenous inhibitors of the Na-K-ATPase, suggesting a primary paracrin or cellular mechanism. We have demonstrated that two different isoforms of the Na-K-ATPase are coexpressed all along the rat nephron. In the puromycin-induced nephrotic syndrome, the activity of one isoform is specifically enhanced. These results demonstrate that the different isoforms of the Na-K-ATPase can be individually controlled.
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PMID:[Role of tubular Na-K-ATPase in nephrotic syndrome induced by puromycin in the rat]. 798 51

To elucidate the mechanism of Na+ retention by insulin in vivo, the direct tubular effect of insulin on NaCl transport in the in vitro microperfused medullary thick ascending limb of Henle (MTAL) was examined. Insulin at 10(-6) mol/l in the bath increased transepithelial voltage (Vte) from 3.1 +/- 0.3 to 5.7 +/- 0.3 mV (n = 12, P < 0.0001). The effect of insulin on Vte was dependent on its concentration, and the half-maximal effect of insulin was observed at 5 x 10(-9) mol/l. Insulin at 10(-6) mol/l also caused a significant decrease of luminal Cl- concentration from 85.4 +/- 5.0 to 62.8 +/- 3.0 mmol/l (n = 5, P < 0.002) when the lumen was microperfused constantly at less than 1 nl/min. Insulin at 10(-6) mol/l also increased net lumen-to-bath Cl- flux (JCl) from 143 +/- 15 to 292 +/- 37 pmol.mm-1.min-1 (n = 5, P < 0.004). When the Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the basolateral membrane was blocked by 10(-4) mol/l ouabain, the insulin-mediated increase in Vte was completely suppressed. When the Na(+)-K(+)-2Cl- cotransporter in the luminal membrane of the MTAL was blocked by 10(-4) mol/l furosemide, the insulin-mediated increase in Vte was also abolished. To test whether adenosine 3',5'-cyclic monophosphate (cAMP) contributes to the action of insulin, we examined the effect of cAMP analogue and cAMP-dependent protein kinase inhibitor on the action of insulin. A maximal concentration (5 x 10(-4) mol/l) of dibutyryl-cAMP (DBcAMP) increased Vte and JCl.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin stimulates NaCl transport in isolated perfused MTAL of Henle's loop of rabbit kidney. 806 87


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