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

---

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

The characteristics of ATP-driven proton and osmotic water transport were studied in endocytic vesicles isolated from rat kidney proximal tubule labelled in vivo with fluorescein isothiocyanate-dextran (FITC-dextran). ATP-driven proton transport was measured from the time course of endosome pH following addition of external ATP. The rate of endosome acidification and the minimum pH were dependent on the ATP concentration. At an initial endosome pH of 7.4, the final pH values were 7.30, 6.99, 6.68, 6.38 and 6.39 at [ATP] = 0.005, 0.05, 0.5, 5 and 10 mmol/L, respectively. The acidification was inhibited by 97% at 0.5 mmol/L N-ethylmaleimide but was not affected by vanadate and oligomycin. Osmotic water permeability was determined in the same endosomes from the rapid kinetics of FITC-dextran fluorescence following an inward sucrose gradient. The osmotic water permeability coefficient was 0.03 cm/s at 23 degrees C. Water permeability was inhibited by 70% with addition of 0.5 mmol/L mercuric chloride. The inhibition was reversed completely by adding 5 mmol/L mercaptoethanol. These data demonstrate that proximal tubule endosomes contain a proton ATPase and water channel. The endocytic process may be important for regulation of acidification and fluid resorption in the proximal tubule.
...
PMID:[Characterization of proton pump and osmotic water transport in endocytic vesicles from rat kidney proximal tubule]. 214 10

The enzyme L-amino acid decarboxylase (L-AADC), found in abundance in rat proximal tubule cell cytosol, converts L-dopa to dopamine. Dopamine, in turn, suppresses proximal tubule sodium transport by inhibiting Na(+)-K(+)-ATPase activity. We sought to determine whether changes in dietary sodium intake in rats lead to adaptation of dopamine formation and dopamine-induced Na(+)-K(+)-ATPase inhibition. In rats on a high-salt (HS) diet, the maximal velocity (Vmax) of renal cortical L-AADC was 78 +/- 19% higher than that in rats on a low-salt (LS) diet. The Michaelis constant (Km) of the enzyme remained unchanged. In renal cortical tubule cell suspensions the L-dopa-induced inhibition of ouabain-sensitive oxygen consumption (QO2) was significantly greater in rats on HS diet than in rats on LS diet. Furthermore, L-dopa completely inhibited the nystatin-induced rise in QO2 in the HS but not in the LS group. Carbidopa, an inhibitor of L-AADC, abolished the L-dopa-induced inhibition of nystatin-stimulated QO2 in cells from HS rats and was without significant effect in cells from LS rats. L-Dopa-stimulated K+ efflux was greater in cells from HS rats at 28 +/- 1 nmol.min-1.mg protein-1, compared with 7 +/- 6 nmol.min-1.ng protein-1 in cells from LS rats. By contrast, ouabain-stimulated K+ efflux did not differ between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Influence of Na+ intake on dopamine-induced inhibition of renal cortical Na(+)-K(+)-ATPase. 215 26

We previously reported a novel rat membrane protein that exhibits a voltage-dependent potassium channel activity on the basis of molecular cloning combined with an electrophysiological assay. This protein, termed IsK protein, is small and different from the conventional potassium channel proteins but induces selective permeation of potassium ions on its expression in Xenopus oocytes. In this investigation, we examined cellular localization of rat IsK protein by preparing three different types of antibody that specifically reacts with a distinct part of rat IsK protein. Immunohistochemical analysis using these antibody preparations demonstrated that rat IsK protein is confined to the apical membrane portion of epithelial cells in the proximal tubule of the kidney, the submandibular duct and the uterine endometrium. The observed tissue distribution of rat IsK protein was consistent with that of the IsK protein mRNA determined by blot hybridization analysis. In epithelial cells, the sodium, potassium-ATPase pump in the basolateral membrane generates a sodium gradient across the epithelial cell and allows sodium ions to enter the cell through the apical membrane. Thus, taking into account the cellular localization of the IsK protein, together with its electrophysiological properties, we discussed a possible function of the IsK protein, namely that this protein is involved in potassium permeation in the apical membrane of epithelial cells through the depolarizing effect of sodium entry.
...
PMID:Immunohistochemical study of a rat membrane protein which induces a selective potassium permeation: its localization in the apical membrane portion of epithelial cells. 215 81

Oxygen consumption (QO2) and net K+ transport were studied in rabbit proximal tubule suspensions to define the early effects of cisplatin on proximal tubule function. Cisplatin caused dose-dependent inhibition of QO2, which was delayed in onset. The concentration of cisplatin required for inhibition decreased as the duration of exposure was increased [40-min exposure, threshold concentration of 10(-4) M, inhibitor constant (Ki) of 10(-3) M; 4-h exposure, threshold concentration of 3 X 10(-5) M, Ki of 10(-4) M]. Both ouabain-sensitive and ouabain-insensitive QO2 were reduced, indicating inhibition of all adenosinetriphosphatases, including Na(+)- K(+)-ATPase activity. There was a parallel fall in ouabain-sensitive net K+ transport and cytosolic K+ content, confirming the latter observation. Na(+)-K(+)-ATPase activity was unchanged in cell membranes prepared by hypotonic lysis from cisplatin-treated tubules, indicating an indirect cytosol-dependent mechanism of enzyme inhibition. Nystatin-stimulated QO2 was reduced in cisplatin-treated tubules, excluding inhibition of Na+ entry as the mechanism of injury and suggesting mitochondrial injury. The latter was confirmed by measurement of carbonylcyanide-m-chlorophenylhydrazone (CCCP)-uncoupled QO2 in intact cells and ADP-stimulated (state 3) QO2 in digitonin-permeabilized tubules. Furthermore, by maximally stimulating mitochondrial respiration with CCCP and nystatin, it was possible to demonstrate mitochondrial injury at a time when basal QO2 and K+ transport were apparently normal. These data suggest that mitochondrial injury is a central event in cisplatin toxicity to the proximal tubule.
...
PMID:Mitochondrial injury: an early event in cisplatin toxicity to renal proximal tubules. 215 14

Previous studies have demonstrated a Na(+)-dependent decrease in the ATP-generated acidification of endosomes and have attributed it to the presence of either a Na(+)-H+ exchanger or a Na(+)-K(+)-adenosinetriphosphatase (ATPase) in parallel with the vacuolar H(+)-ATPase. In the present study we have examined the possibility that both of these two Na+ transporters might be present in endosome-enriched microsomes isolated from rabbit renal cortex. After the establishment of a stable pH gradient by ATP in this preparation, addition of Na+ induced a decrease in the pH gradient. Expression of this effect of Na+ did not require the presence of ATP or K+. Choline and K+ had no effect on the ATP-dependent pH gradient, but addition of Li+ caused a small reduction in the pH gradient. Amiloride, ouabain, and vanadate had no effect on the Na(+)-induced dissipation of the ATP-driven pH gradient. In addition, a pH gradient-dependent 22Na+ uptake by the endosomal vesicles that was insensitive to amiloride, ouabain, or vanadate was demonstrated. These results provide evidence against the presence of a Na(+)-K(+)-ATPase in endosome-enriched microsomes from the renal cortex and support the existence of an amiloride-insensitive Na(+)-H+ exchanger in parallel with the vacuolar H(+)-ATPase. This endosomal Na(+)-H+ exchanger might have important implications for the regulation of vacuolar H(+)-ATPase activity as well as proximal tubule acidification.
...
PMID:Na(+)-H+ exchange, but not Na(+)-K(+)-ATPase, is present in endosome-enriched microsomes from rabbit renal cortex. 215 20

Ouabain-sensitive (OS) O2 consumption was determined in proximal tubular cells from weanling rats fed 21% (normal-protein, NP) or 50% (high-protein, HP) protein diet for 4 days. Butyric acid 10(-3)M was added as a substrate for mitochondrial respiration and the ionophore amphotericin B (10 micrograms ml-1) was used to sodium-load the cells. OS respiration was higher in HP than in NP cells in both DME and amino acid-free electrolyte solution (ES). Amphotericin B significantly increased OS respiration in both NP and HP cells, implying that the Na-K pump was activated by increased intracellular Na. In cells incubated in ES, addition of amino acids stimulated OS respiration significantly in HP cells (16.9 +/- 1.4 vs 21.2 +/- 1.1 nmol min-1 mg-1 protein) and in NP cells (13.9 +/- 0.3 vs 14.9 +/- 0.6 nmol min-1 mg-1 protein). Stimulation was significantly higher in HP cells (26 +/- 4%) than in NP cells (7 +/- 4%) (P less than 0.001). The amino acids did not stimulate ouabain-insensitive respiration. The results indicate that an HP diet to weanling rats will increase proximal tubule cell Na, K-ATPase-dependent respiration by enhancing Na entry via the Na-amino acid symports.
...
PMID:Amino acid stimulation of Na,K-ATPase activity in rat proximal tubule after high-protein diet. 216 22

In this review we have summarized the work of ourselves and others on ionic and hormonal regulation of synthesis of the sodium pump. No one central theme emerges from this summary. Rather, it appears that abundance can be regulated pre-translationally or posttranslationally. As reviewed recently, regulation of the expression of the beta glycoprotein subunit, which has no described enzymatic function, can regulate holoenzyme expression. In the kidney this is exemplified in our studies in LLC-PK1 cells and proximal tubule cells where pre-translational regulation of beta expression is key to increasing holoenzyme abundance, and also exemplified in the hypothyroid renal cortex where regulation of beta protein abundance post-translationally appears to impact the abundance of enzymatically active NaK-ATPase. Future studies in the field of ionic regulation of NaK-ATPase must be directed at elucidating the signals that mediate the response, and at how these signals alter the NaK-ATPase biosynthetic pathway from expression of alpha and beta genes, through to turnover of the mature NaK-ATPase heterodimer.
...
PMID:Ionic regulation of the biosynthesis of NaK-ATPase subunits. 216 28

This study examines the role of endogenous dopamine (DA) for the regulation of renal tubular sodium (Na) transport. The enzyme L-amino acid decarboxylase (L-AADC) that converts L-dopa to DA has been localized to the proximal tubule cells with immunocytochemistry. Locally formed DA will inhibit the activity of Na-K-ATPase, the enzyme that yields energy to active Na transport. The effect is of physiological importance during high salt diet. The phosphoprotein DARPP-32, a DA1 receptor associated third messenger is abundant in the medullary thick ascending limb of Henle (mTAL). DARPP-32 is phosphorylated after activation of DA1 receptors. DARPP-32 is in its phosphorylated form a potent phosphatase inhibitor. Activation of the DA1 receptor in mTAL with the DA1 agonist SKF 82526 causes dose-dependent inhibition of Na-K-ATPase activity. The effect involves activation of cAMP protein kinase. It is likely that this effect is potentiated by DARPP-32.
...
PMID:The significance of L-amino acid decarboxylase and DARPP-32 in the kidney. 216 32

The short term regulation of the activity of the Na,K-pump (Na+,K(+)-ATPase) is just beginning to be understood. By using single microdissected proximal tubule segments (PCT) (permeabilized in order to clamp Na entry), it was possible to study regulation of Na+,K(+)-ATPase activity in its own environment and in a well defined cell population. The Na+,K(+)-ATPase activity can be regulated over a short term via guanidine triphosphate (GTP) dependent regulatory proteins. However the guanidine proteins are not directly coupled to the Na,K-pump and the mechanism involves the activation of complex intracellular signalling system. Locally produced dopamine induces a dose dependent inhibition of Na+,K+ ATPase activity. This inhibition is mediated by a complex mechanism that requires the activation of both membrane dopamine receptors, DA-1 and DA-2. It involves the activation of a pertussis toxin sensitive GTP-binding protein and activation of protein kinase C. A DA-2 agonist only inhibits Na+,K(+)-ATPase activity when it is incubated together with dibutyryl cAMP or Forskolin. We have therefore concluded that an increase in cellular cAMP levels plays a permissive role for DA-2 inhibition of Na+,K(+)-ATPase activity. A fully differentiated cell is required for dopamine inhibition of Na+,K(+)-ATPase activity. An abnormal regulation of proximal tubule Na+,K(+)-ATPase activity might be of importance in the pathogenesis of certain types of hypertension.
...
PMID:Short-term regulation of Na+,K(+)-ATPase activity by dopamine. 216 34

Increased renal nerve activity and sodium retention have been implicated in the development of hypertension in genetically transmitted forms of this disease. The present studies were designed to investigate the relationship between renal nerve integrity and renal proximal tubule (Na+, K+)-ATPase activity in spontaneously hypertensive rats (SHR). (Na+, K+)-ATPase activity of basolateral membranes (BLMs) enriched from proximal tubules of five-week-old SHR was greater, 328.6 +/- 18.9 nmol Pi/mg protein.min, than in age-matched genetic controls rats (Wistar-Kyoto, WKY, rats), 262.3 +/- 34.6 nmol Pi/mg protein.min (P less than 0.02). There was no detectable difference in (Na+, K+)-ATPase activity of 13-week-old SHR and WKY rats. Prior renal denervation was associated with a reduction in proximal tubule basolateral membrane (BLM) (Na+, K+)-ATPase activity, 316.8 +/- 23.8 to 223.1 +/- 23.9 nmol Pi/mg protein/min (P less than 0.02), in five-week SHR. However, denervation had no effect on renal (Na+, K+)-ATPase activity in either WKY rats, nor did sham-denervation in SHR. In addition, exogenous norepinephrine, 1 microM, produced a more pronounced stimulation of (Na+, K+)-ATPase activity in basolateral membranes from SHR as opposed to WKY controls (40.2% vs. 28.7%). Therefore, renal nerve integrity and exogenous catecholamines have a greater stimulatory influence on proximal tubule (Na+, K+)-ATPase activity in the early stages (prior to 5 weeks) of the development of hypertension in SHR than in age-matched WKY rats.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Adrenergic regulation of (Na+, K+)-ATPase activity in proximal tubules of spontaneously hypertensive rats. 217 14


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---