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 distal tubule, which includes the thick ascending limb (TAL), the macula densa, and the distal convoluted tubule (DCT), and the collecting duct are structurally heterogeneous, thus reflecting the functional heterogeneity that is also present. As the TAL ascends from medulla to cortex, the surface area of the apical plasma membrane increases while that of the basolateral membrane decreases. The structure of the DCT resembles that of the medullary TAL. An excellent correlation exists between structure, Na-K-ATPase activity, and NaCl reabsorptive capacity in the distal tubule. The collecting duct is subdivided into the initial collecting tubule (IC), and cortical (CCD), outer medullary (OMCD), and inner medullary (IMCD) collecting ducts. Between the distal tubule and the collecting duct is a transition region termed the connecting segment or connecting tubule (CNT). Considerable structural heterogeneity exists along the collecting duct within the two major cell populations, the intercalated cells and the principal cells. In the CNT, the ICT, and the CCD, potassium loading and mineralocorticoids stimulate Na-K-ATPase activity and cause proliferation of the basolateral membrane of CNT cells and principal cells, thus identifying the cells responsible for mineralocorticoid-stimulated potassium secretion in these regions. Finally, at least two morphologically distinct populations of intercalated cells exist, types A and B. In the rat, type A predominates in the CNT and the OMCD and is believed to be responsible for H+ secretion, at least in the OMCD. Type B predominates in the CCD, where it may be involved in bicarbonate secretion.
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PMID:Structural-functional relationship along the distal nephron. 352 38

The respective effects of aldosterone and arginine vasopressin (AVP) were examined on the number of active Na(+)-K(+)-ATPase and their pumping activity in nonperfused microdissected mouse cortical collecting tubules (CCD) by measuring specific 3H-ouabain binding and ouabain-sensitive 86Rb uptake. In adrenalectomized (ADX) animals, incubation of CCD with AVP (10(-8) M for 5 min) had no effect on the number of pumps. In contrast, in ADX animals replete with aldosterone, AVP induced a approximately equal to 40% increase in the number of pumps. This was accompanied by a approximately equal to 60-65% increase in ouabain-sensitive Rb uptake. AVP effect was dose-dependent (10(-10)-10(-8) M) and was reproduced by dDAVP, forskolin and 8-Br cAMP, indicating a V2 pathway. It was inhibited by amiloride 10(-5) M, and did not occur in CCD incubated in hyperosmotic solution, suggesting that the signal was transmitted via apical sodium entry and cell swelling. Finally, the AVP-dependent increase in the number of pumps was rapid (within 5 min) and transient (< 25 min). These results demonstrate that, in the CCD, aldosterone and AVP act synergistically to increase not only the apical sodium entry but also the basolateral Na(+)-K(+)-ATPase transport capacity: AVP allows a rapid recruitment and/or activation of an aldosterone-dependent pool of latent Na(+)-K(+)-ATPase.
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PMID:Synergistic action of vasopressin and aldosterone on basolateral Na(+)-K(+)-ATPase in the cortical collecting duct. 763 89

The distribution of transcripts encoding the gastric H(+)-K(+)-adenosinetriphosphatase (ATPase) alpha-subunit in the normal rat kidney was studied by reverse transcription-polymerase chain reaction (RT-PCR), combined with DNA sequence analysis and renal microdissection, and by nonradioactive in situ hybridization of fixed kidney sections using highly specific molecular probes. RT-PCR products corresponding to the gastric H(+)-K(+)-ATPase alpha-subunit were detected in the cortex, outer and inner medulla, and in isolated cortical (CCD) and inner medullary collecting ducts (IMCD). With digoxigenin-labeled cRNAs derived from the 5' and 3' ends of the gastric H(+)-K(+)-ATPase alpha-subunit cDNA, specific hybridization signal was detected prominently in all the cells of the connecting segment and CCD, the intercalated cells of the outer medullary collecting duct, the IMCD, and the renal pelvic epithelium lining the secondary pouches. Weak labeling was noted in the S3 segment of the proximal tubule, the distal convoluted tubule, and the cortical thick ascending limb of Henle. Hybridization with the sense probes produced no cellular labeling. These data provide the first direct demonstration for the expression and cellular distribution of mRNA encoding the gastric H(+)-K(+)-ATPase alpha-subunit in the normal, potassium-replete kidney, and they provide essential tools for the molecular analysis of renal acid base and potassium transport under physiological and pathophysiological conditions.
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PMID:Expression and cellular localization of mRNA encoding the "gastric" isoform of H(+)-K(+)-ATPase alpha-subunit in rat kidney. 784 Feb 53

This study was undertaken to evaluate the effect of long-term diabetes on Na(+)-K(+)-ATPase in isolated nephron segments in five groups of rats: 1) controls of 7 wk duration (7 WD), 2) diabetes mellitus (DM) of 7 WD, 3) DM of 7 WD treated with insulin replacement, 4) DM rats of 25 WD, and 5) control rats of 25 WD. The blood glucose (BG) values in the first three groups were 123 +/- 9, 450 +/- 25, and 302 +/- 30 mg/dl; the glomerular filtration rate (GFR) was 1.34 +/- 0.08, 1.80 +/- 0.10, and 1.77 +/- 0.08 ml/min; and urinary sodium excretion was 0.94 +/- 0.05, 1.76 +/- 0.10, and 1.40 +/- 0.07 mu eq/min. Na(+)-K(+)-ATPase in group 2 increased in all segments studied (P < 0.001, group 1 vs. 2 for all). In group 3, Na(+)-K(+)-ATPase normalized in proximal convoluted (PC), proximal straight (PS), and distal convoluted (DC) tubules (P < 0.001, group 2 vs. group 3 for all), whereas in the outer medullary thick ascending limb (OMTAL) the correction was partial and in the CTAL and CCD there was no correction. In group 4 BG was 420 +/- 20 mg/100 ml compared with 123 +/- 9 in group 5 (P < 0.001), and GFR was 1.19 +/- 0.11 ml/min vs. 1.15 +/- 0.11 in group 5 (P = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal tubular Na(+)-K(+)-ATPase in diabetes mellitus: relationship to metabolic abnormality. 839 94

The A cell may possess multiple H+ transporters, including H(+)-adenosinetriphosphatase (H(+)-ATPase) and H(+)-K(+)-ATPase. The current study examines the relative roles of proton transporters in the A cell by observing their contribution to both basal intracellular pH (pHi) regulation and pHi recovery from an intracellular acid load. CCD were studied using in vitro microperfusion, and pHi was measured in the individual A cell using the fluorescent, pH-sensitive dye, 2',7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein (BCECF). Inhibiting H(+)-ATPase with luminal bafilomycin A1 decreased basal pHi, whereas inhibiting apical H(+)-K(+)-ATPase with either luminal Sch-28080 or luminal potassium removal did not. The predominant mechanism of pHi, recovery from an intracellular acid load was peritubular sodium dependent and peritubular ethylisopropylamiloride (EIPA) sensitive, identifying basolateral Na+/H+ exchange activity. In the absence of peritubular sodium, pHi recovery was inhibited by luminal bafilomycin A1 but not by luminal Sch-28080 addition or by luminal potassium removal. However, when Na+/H+ exchange was inhibited with EIPA, both bafilomycin A1 sensitive and potassium dependent, Sch-28080-sensitive components of pHi recovery were present. Quantitatively, the rate of H(+)-ATPase proton secretion was greater than the rate of H(+)-K(+)-ATPase proton secretion. We conclude that basolateral Na+/H+ exchange is the predominant mechanism of A cell pHi recovery from an intracellular acid load. An apical H(+)-ATPase is the primary apical transporter contributing to A cell pHi regulation. An apical H(+)-K(+)-ATPase, while present, plays a more limited role under the conditions tested.
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PMID:Intracellular pH regulation in the rabbit cortical collecting duct A-type intercalated cell. 932 6

The compensatory hypertrophy in different renal cortical structures was studied in rats 10 and 21 days after unilateral nephrectomy (UNX). Quantitative morphological/stereological analysis revealed significant increases in total renal cortical volume--33% on day 10 and 48% on day 21--after UNX. These changes were paralleled by significant increments in the volumes of proximal convoluted tubule (PCT, 55%), distal convoluted tubule (DCT, 114%), and cortical collecting duct (CCD, 106%) segments on day 10. The corresponding changes on day 21 were 76, 122, and 212%, respectively. These alterations were accompanied by increases in segment length; 3% PCT, 23% DCT, and 50% CCD on day 10 and 9% PCT, 30% DCT, and 142% CCD on day 21 after UNX. The total luminal and basolateral cell membrane surface areas also exhibited a time-dependent increase after UNX. The increments in both luminal and basolateral membrane domains in PCT and DCT after 10 days were not significant, but reached significance after 21 days (PCT: luminal membrane 21%, basolateral membrane 63%; DCT: luminal membrane 98%, basolateral membrane 63%). In contrast, CCD membrane areas had increased substantially already 10 days after UNX (luminal membrane 92%, basolateral membrane 71%). It declined subsequently by day 21 (luminal membrane 57%, basolateral membrane 32%). The cell rubidium concentration after a 30-second rubidium infusion, an index of Na-K-ATPase activity, as well as sodium concentrations were unaltered in cells of all nephron segments investigated. Altogether the stereological analysis shows that the compensatory increase in organ volume can be attributed primarily to an increase in nephron epithelial volume. The PCT responds with 'radial' hypertrophy (thickening of the tubular epithelial wall), while the DCT undergoes 'length' hypertrophy (increase of tubular length without thickening of the tubular wall and without an increase in number of cells). This type of hypertrophy is especially prominent on day 21 after UNX for the CCD which doubles in length. Only on day 10 does the CCD seem to respond with hyperplasia. Adaptive changes in response to UNX develop gradually. Only a few of the morphological parameters studied had completed their change by 10 days, the majority required longer.
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PMID:Quantitative morphology of renal cortical structures during compensatory hypertrophy. 969 94

The physiological activity of osteoblasts is known to be closely related to increased intracellular Ca2+ activity ([Ca2+]i) in osteoblasts. The cellular regulation of [Ca2+]i in osteoblasts is mediated by Ca2+ movements associated with Ca2+ release from intracellular Ca2+ stores, and transmembrane Ca2+ influx via Na+-Ca2+ exchanger, and Ca2+ ATPase. Reactive oxygen species, such as H2O2, play an important role in the regulation of cellular functions, and act as signaling molecules or toxins in cells. In this study, we investigated the effects of H2O2 on cellular Ca2+ regulation in osteoblasts by measuring intracellular Ca2+ activities using cellular calcium imaging techniques. Osteoblasts were isolated from the femurs and tibias of neonatal rats, and cultured for 7 days. The cultured osteoblasts were loaded with a Ca2+-sensitive fluorescent dye, Fura-2, and fluorescence images were monitored using a cooled CCD camera, and subsequently analyzed using image analyzing software. The results obtained are as follows: (1) The osteoblasts with lower basal Ca2+ activities yielded a transient Ca2+ increase, a Ca2+ spike, while osteoblasts with higher basal Ca2+ activities showed a continuous increase in [Ca2+]i leading to cell death. (2) Ca2+ spikes, generated after removing Na+ from superfusing solutions, were blocked by H2O2 and this was followed by a sustained increase in Ca2+ activity. (3) ATP- induced Ca2+ spikes were inhibited by pretreating with H2O2 and this was followed by a continuous increase of [Ca2+]i. When cells were pretreated with the exogenous nitric oxide (NO) donor S-Nitroso-N-acetylpenicilance (SNAP, 50 microM), treatments of ATP (1 mM) induced a Ca2+ spike-like increase, but [Ca2+]i did not return to the basal level. (4) The expression of inositol- 1,4,5-triphosphate receptor (IP3R) was enhanced by H2O2. Our results suggest that H2O2 modulates intracellular Ca2+ activity in osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores.
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PMID:H2O2 enhances Ca2+ release from osteoblast internal stores. 1197 Dec 17

The present clinical taxonomy of distal renal tubular acidoses includes "gradient," "secretory," and "voltage" defects. These categories refer to presumed collecting duct defects in which the epithelium may be abnormally permeable and unable to sustain an ion gradient, in which luminal proton ATPases are defective, or in which electrogenic Na+ reabsorption is impaired and luminal electronegativity is reduced. Classification of affected individuals is based on urinary pH and ion concentrations during spontaneous acidosis and during SO(4)(2-) infusion, as well as urinary PCO2 during HCO(3)(-) loading. A model of rat CD has been developed that has been used to examine determinants of urinary acidification (Weinstein AM. Am J Physiol Renal Physiol 283: F1252-F1266, 2002) and the interplay of HCO(3)(-) and PO(4)(3-) loads to generate a disequlibrium pH and equilibrium PCO2. In this paper, pure forms of gradient, voltage, and secretory defects are simulated, with attention to variability in the locus of the defect in the cortical (CCD), outer medullary (OMCD), or inner medullary collecting duct (IMCD). The objective of these calculations is to discover whether the intuitive description of these defects is sustained quantitatively. The most important positive finding is that the locus of the transport defect along the CD plays a critical role in the apparent severity of the lesion, with more proximal defects being less severe and more easily correctable. In particular, model calculations suggest that for gradient or secretory defects to be clinically detectable they need to involve the OMCD and/or IMCD. Additionally, the calculations reveal a possible mechanism for CD K+ wasting, which does not involve failure of H+ - K+-ATPase but derives from a paracellular anion leak and thereby a more electronegative lumen. The most important negative finding is the lack of support for the category of renal tubular acidosis associated with a voltage defect. Although CD lesions that present with both K+ and H+ secretory defects suggest mediation by transepithelial electrical potential difference (PD), both PD changes and proton pump PD sensitivity appear too small to account for the observed abnormalities.
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PMID:A mathematical model of rat collecting duct. III. Paradigms for distal acidification defects. 1238 80

Previous studies have shown that the newly found endogenous inhibitor (NCX(IF)) of the cardiac Na/Ca exchanger (NCX1) is capable of regulating the muscle strip's contractility and relaxation. Here, the effects of purified NCX(IF) were tested on single cell shortening-lengthening (by using the IR CCD camera coupled with the two-edge video-detector) and [Ca]i-transients (by monitoring the changes in fluo-3 fluorescence). A perfusion of isolated cardiomyocytes (paced at 0.5-1.0 Hz) with NCX(IF) results in 4-6-fold enhancement in the amplitude of cell shortening-lengthening reaching the steady-state levels within 5-8 min (n=20, p<0.009). Simultaneous recordings of cell shortening-lengthening and [Ca]i-transients from the same cell show that the amplitude enhancement is associated with accelerated decay of both signals. Therefore, the NCX(IF)-dependent modulation of the single cell contractility is primarily governed by Ca-related mechanisms. The observed data are consistent with a proposal suggesting that the inhibition of NCX1 by NCX(IF) results in Ca-dependent activation of SERCA (SR Ca ATPase), yielding the accelerated decay of the [Ca]i-transients. The subsequent increase in the SR Ca content may result in enhanced Ca-release reflecting the manifested promotion of [Ca]i-transients. More systematic study is required for confirming this working hypothesis.
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PMID:Purified endogenous inhibitor of the Na/Ca exchanger can enhance the cardiomyocytes contractility and calcium transients. 1678 52

Final urinary acidification is achieved by electrogenic vacuolar H(+)-ATPases expressed in acid-secretory intercalated cells (ICs) in the connecting tubule (CNT) and the cortical (CCD) and initial medullary collecting duct (MCD), respectively. Electrogenic Na(+) reabsorption via epithelial Na(+) channels (ENaCs) in the apical membrane of the segment-specific CNT and collecting duct cells may promote H(+)-ATPases-mediated proton secretion by creating a more lumen-negative voltage. The exact localization where this supposed functional interaction takes place is unknown. We used several mouse models performing renal clearance experiments and assessed the furosemide-induced urinary acidification. Increasing Na(+) delivery to the CNT and CCD by blocking Na(+) reabsorption in the thick ascending limb with furosemide enhanced urinary acidification and net acid excretion. This effect of furosemide was abolished with amiloride or benzamil blocking ENaC action. In mice deficient for the IC-specific B1 subunit of the vacuolar H(+)-ATPase, furosemide led to only a small urinary acidification. In contrast, in mice with a kidney-specific inactivation of the alpha subunit of ENaC in the CCD and MCD, but not in the CNT, furosemide alone and in combination with hydrochlorothiazide induced normal urinary acidification. These results suggest that the B1 vacuolar H(+)-ATPase subunit is necessary for the furosemide-induced acute urinary acidification. Loss of ENaC channels in the CCD and MCD does not affect this acidification. Thus, functional expression of ENaC channels in the CNT is sufficient for furosemide-stimulated urinary acidification and identifies the CNT as a major segment in electrogenic urinary acidification.
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PMID:The connecting tubule is the main site of the furosemide-induced urinary acidification by the vacuolar H+-ATPase. 1708 Jan 56


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