Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian distal colon, which is composed of different cell types, actively transports Na, K and Cl in absorptive and K and Cl in secretory directions. To further characterize the K absorption process and to identify the cells involved in K absorption, unidirectional Rb fluxes and luminal Rb uptake into different epithelial cell types were determined in isolated guinea-pig distal colon. Net Rb absorption (1.5-2.5 micromol.h-1.cm-2) was not influenced by inhibition of Na transport with amiloride or by incubating both sides of the epithelium with Na-free solutions, but was almost completely abolished by luminal ouabain, ethoxzolamide or by incubating both sides of the epithelium with Cl-free solutions. Luminal Rb uptake, blockable by luminal ouabain, preferentially occurred in columnar surface and neck cells, to a lesser extent in surface goblet cells and to an insignificant degree in lower crypt cells. Employing a luminal Rb-Ringer (5.4 mM Rb) the Rb concentration increased within 10 min in columnar surface and neck, surface goblet and lower crypt cells to 70, 32 and about 10 mmol. kg-1 wet weight, respectively. The presence of 5.4 mM K in the luminal incubation solution reduced Rb uptake almost completely indicating a much higher acceptance of the luminal H-K-ATPase for K than for Rb. The increase in Na and decrease in K concentrations in surface and neck cells induced by luminal ouabain might indicate inhibition of the basolateral Na-K-ATPase or drastic enhancement of cellular Na uptake by the Na-H exchanger. Bilateral Na-free incubation did not alter Rb uptake, but bilateral Cl-free incubation drastically reduced it. Inhibition of net Rb absorption by ethoxzolamide and inhibition of both Rb absorption and Rb uptake by bilateral Cl-free incubation support the notion that cellular CO2 hydration is a necessary prerequisite for K absorption and that HCO3 leaves the cell via a Cl-HCO3 exchanger. Since ouabain-inhibitable transepithelial Rb flux and luminal Rb uptake rate by surface and neck cells were about the same, Rb(K) absorption seems to be accomplished mainly by columnar surface cells.
 ...
PMID:Cellular site of active K absorption in the guinea-pig distal colonic epithelium. 959 29

A mathematical model of the inner medullary collecting duct (IMCD) of the rat has been developed that is suitable for simulating luminal buffer titration and ammonia secretion by this nephron segment. Luminal proton secretion has been assigned to an H-K-ATPase, which has been represented by adapting the kinetic model of the gastric enzyme by Brzezinski et al. (P. Brzezinski, B. G. Malmstrom, P. Lorentzon, and B. Wallmark. Biochim. Biophys. Acta 942: 215-219, 1988). In shifting to a 2 H+:1 ATP stoichiometry, the model enzyme can acidify the tubule lumen approximately 3 pH units below that of the cytosol, when luminal K+ is in abundance. Peritubular base exit is a combination of ammonia recycling and HCO3- flux (either via Cl-/HCO3- exchange or via a Cl- channel). Ammonia recycling involves NH4(+) uptake on the Na-K-ATPase followed by diffusive NH3 exit [S. M. Wall. Am. J. Physiol. 270 (Renal Physiol. 39): F432-F439, 1996]; model calculations suggest that this is the principal mode of base exit. By virtue of this mechanism, the model also suggests that realistic elevations in peritubular K+ concentration will compromise IMCD acid secretion. Although ammonia recycling is insensitive to carbonic anhydrase (CA) inhibition, the base exit linked to HCO3- flux provides a CA-sensitive component to acid secretion. In model simulations, it is observed that increased luminal NaCl entry increases ammonia cycling but decreases peritubular Cl-/HCO3- exchange (due to increased cell Cl-). This parallel system of peritubular base exit stabilizes acid secretion in the face of variable Na+ reabsorption.
 ...
PMID:A mathematical model of the inner medullary collecting duct of the rat: acid/base transport. 961 22

Hot beverages expose the esophageal epithelium to temperatures as high as 58 degrees C. To study the impact of such temperatures, rabbit esophageal epithelium was exposed to luminal heat or both luminal and serosal heat while mounted in Ussing chambers. Luminal heat, mimicking exposure to hot beverages, reduced potential difference (PD) and resistance (R) when applied at >/=49 degrees C and reduced short-circuit current (Isc) at >/=60 degrees C. At >/=60 degrees C, subepithelial blisters developed. Higher temperatures reduced R only moderately and reversibly. In contrast, the Isc declined sharply and irreversibly once threshold was reached. Luminal and serosal heat also reduced PD, Isc, and R, although the threshold for reduction in Isc was now similar to that for R. Additionally, luminal and serosal heat reduced Isc more than R for any given temperature and resulted in blisters at lower temperatures (50 degrees C) than luminal heat alone. The heat-induced decline in Isc was attributed in part to inactivation of Na-K-ATPase activity, although other transport systems could have been equally affected, and the decline in R to an increase in paracellular permeability. The latter effect on R also contributed to an increase in tissue sensitivity to luminal acid damage. Consumption of hot beverages exposes the esophagus to temperatures that can negatively impact epithelial structure and function. Impaired barrier function by heat increases the risk of esophageal damage by subsequent contact with (refluxed) gastric acid. These findings help explain in part the association between esophageal disease and consumption of hot beverages.
 ...
PMID:Effect of heat stress on rabbit esophageal epithelium. 1036 35

Acute as well as chronic exposure of cadmium (Cd) leads to proximal tubule injury. The exact cellular mechanism of this disorder and whether there is a contribution of cadmium-metallothionein (Cd-MT), a binding protein of Cd, remain unclear. We perfused isolated S2 segments of rabbit nephron, and the deflections of transmural voltage (DeltaV(t)) and apical membrane voltage (DeltaV(a)) on elimination of glucose or alanine from the perfusate were measured for the parameters of activity of Na(+)-glucose and Na(+)-amino acid cotransporters. The effects of Cd-MT or CdCl(2) to either bath or lumen for 10 min on these parameters were examined. We also measured the lumen-to-bath [(14)C]glucose flux. Addition of Cd-MT to lumen suppressed glucose- or alanine-dependent DeltaV(t) and DeltaV(a), as well as baseline V(t) and basolateral membrane voltage (V(b)), at approximately 10 min. [(14)C]glucose flux was inhibited by Cd-MT to lumen. The effects of Cd-MT to bath and CdCl(2) to either lumen or bath were 100-fold less potent than that of Cd-MT to lumen. Luminal Cd-MT immediately suppressed the glucose-dependent DeltaV(a), whereas the baseline V(a) and V(t) were unchanged. The early effect of luminal Cd-MT was simulated by addition of 10(-4) M phloretin. Addition of 10(-4) M ouabain to the bath simulated the later effect of Cd-MT. The protection of SH group by dithiothreitol prevented the early effect of Cd-MT, but not the later effect. We concluded that Cd-MT initially acts directly on Na(+)-glucose and Na(+)-amino acid cotransporters from the lumen by attacking SH group, followed by the later inhibition of Na(+)-K(+)-ATPase after entering the cell from the apical membrane.
 ...
PMID:Acute effect of cadmium-metallothionein on glucose and amino acid transport across the apical membrane of the rabbit proximal tubule perfused in vitro. 1064 Mar 17

Luminal acidification in parts of the male reproductive tract generates an appropriate pH environment in which spermatozoa mature and are stored. The cellular mechanisms of proton (H+) secretion in the epididymis and the proximal vas deferens involve the activity of an apical vacuolar H+ ATPase in specialized cell types, as well as an apical Na+/H+ exchanger in some tubule segments. In this study we used Western blotting and immunocytochemistry to localize the H+ ATPase in various segments of the male reproductive tract in rat and man as a first step toward a more complete understanding of luminal acidification processes in this complex system of tissues. Immunoblotting of isolated total cell membranes indicated a variable amount of H+ ATPase in various segments of the rat reproductive tract. In addition to its known expression in distinct cell types in the epididymis and vas deferens, the H+ ATPase was also localized at the apical pole and in the cytoplasm of epithelial cells in the efferent duct (nonciliated cells), the ampulla of the vas deferens and the ventral prostate (scattered individual cells), the dorsal and lateral prostate, the ampullary gland, the coagulating gland, and all epithelial cells of the prostatic and penile urethra. Both apical and basolateral localization of the protein were found in epithelial cells of the prostatic ducts in the lateral prostate and in periurethral tissue. Only cytoplasmic, mostly perinuclear localization of the H+ ATPase was found in all epithelial cells of the seminal vesicles and in most cells of the ventral prostate and coagulating gland. No staining was detected in the seminiferous tubules, rete testis, and bulbourethral gland. In human tissue, H+ ATPase-rich cells were detected in the epididymis, prostate, and prostatic urethra. We conclude that the vacuolar H+ ATPase is highly expressed in epithelial cells of most segments of the male reproductive tract in rat and man, where it may be involved in H+ secretion and/or intracellular processing of the material endocytosed from the luminal fluid or destined to be secreted by exocytosis.
 ...
PMID:Distribution of the vacuolar H+ atpase along the rat and human male reproductive tract. 1136 98

Vocal fold hydration is critical to phonation. We hypothesized that the vocal fold generates bidirectional water fluxes, which are regulated by activity of the Na(+)-K(+)- ATPase. Western blots and immunohistochemistry demonstrated the presence of the alpha-subunit Na(+)-K(+)-ATPase in the canine vocal fold (n = 11). Luminal cells, basal and adjacent one to two layers of suprabasal cells within stratified squamous epithelium, were immunopositive, as well as basolateral membranes of submucosal seromucous glands underlying transitional epithelia. Canine (n = 6) and ovine (n = 14) vocal fold mucosae exhibited transepithelial potential differences of 8.1 +/- 2.8 and 9.3 +/- 1.3 mV (lumen negative), respectively. The potential difference and short-circuit current (ovine = 31 +/- 4 microA/cm(2); canine = 41 +/- 10 microA/cm(2)) were substantially reduced by luminal administration of 75 microM acetylstrophanthidin (P < 0.05). Ovine (n = 7) transepithelial water fluxes decreased from 5.1 +/- 0.3 to 4.3 +/- 0.3 microl x min(-1) x cm(-2) from the basal to luminal chamber and from 5.2 +/- 0.2 to 3.9 +/- 0.3 microl x min(-1) x cm(-2) from the luminal to basal chamber by luminal acetylstrophanthidin (P < 0.05). The presence of the Na(+)-K(+)-ATPase in the vocal fold epithelium and the electrolyte transport derived from its activity provide the intrinsic mechanisms to regulate cell volume as well as vocal fold hydration.
 ...
PMID:Regulation of vocal fold transepithelial water fluxes. 1150 42

Hydrochloric acid (HCl) is produced in parietal cells of gastric epithelium by a H(+)-K(+) pump. Protons are secreted into the gastric lumen in exchange for K(+) by the action of the H(+)-K(+)-ATPase. Luminal K(+) is essential for the operation of the pump and is thought to be supplied by unidentified K(+) channels localized at the apical membrane of parietal cells. In this study, we showed that histamine- and carbachol-induced acid secretion from isolated parietal cells monitored by intracellular accumulation of aminopyrine was depressed by Ba(2+), an inhibitor of inwardly rectifying K(+) channels. Among members of the inwardly rectifying K(+) channel family, we found with reverse transcriptase-polymerase chain reaction analyses that Kir4.1, Kir4.2 and Kir7.1 were expressed in rat gastric mucosa. With immunohistochemical analyses, Kir4.1 was found to be expressed in gastric parietal cells and localized specifically at their apical membrane. The current flowing through Kir4.1 channel expressed in HEK293T cells was not affected by reduction of extracellular pH from 7.4 to 3. These results suggest that Kir4.1 may be involved in the K(+) recycling pathway in the apical membrane which is required for activation of the H(+)-K(+) pump in gastric parietal cells.
 ...
PMID:Specific localization of an inwardly rectifying K(+) channel, Kir4.1, at the apical membrane of rat gastric parietal cells; its possible involvement in K(+) recycling for the H(+)-K(+)-pump. 1192 62

Luminal acidification is important for the maturation of secretory granules, yet little is known regarding the regulation of pH within them. A pH-sensitive green fluorescent protein (EGFP) was targeted to secretory granules in RIN1046-38 insulinoma cells by using a construct in which the EGFP gene was preceded by the nucleotide sequence for human growth hormone. Stimulatory levels of glucose doubled EGFP secretion from cell cultures, and potentiators of glucose-induced insulin secretion enhanced EGFP release. Thus this targeted EGFP is useful for population measurements of secretion. However, less than ~4% of total cell EGFP was released after 1.5 h of stimulation. Consequently, when analyzed in single cells, fluorescence of the targeted EGFP acts as an indicator of pH within secretory granules. Glucose elicited a decrease in granule pH, whereas inhibitors of the V-type H(+)-ATPase increased pH and blocked the glucose effect. Granule pH also was modified by effectors of the protein kinase A pathway, with activation eliciting granule alkalinization, suggesting that potentiation of peptide release by cAMP may involve regulated changes in secretory granule pH.
 ...
PMID:Regulation of secretory granule pH in insulin-secreting cells. 1210 52

Alendronate, an aminobisphosphonate, produces as a side effect a topical (pill induced) esophagitis. To gain insight into this phenomenon, we assessed the effects of luminal alendronate on both esophageal epithelial structure and function. Sections of rabbit esophageal epithelium were exposed to luminal alendronate at neutral or acidic pH while mounted in Ussing chambers to monitor transmural electrical potential difference (PD), short-circuit current (I(sc)), and resistance (R). Morphological changes were sought by light microscopy in hematoxylin and eosin-stained sections. Impedance analysis was used for localization of alendronate-induced effects on ion transport. Luminal, but not serosal, alendronate (pH 6.9-7.2), increased PD and I(sc) in a dose- and time-dependent manner, with little change in R and mild edema of surface cell layers. The changes in I(sc) (and PD) were reversible with drug washout and could be prevented either by inhibition of Na,K-ATPase activity with serosal ouabain or by inhibition of apical Na channels with luminal acidification to pH 2.0 with HCl. An effect on apical Na channel activity was also supported by impedance analysis. Luminal alendronate at acidic pH was more damaging than either alendronate at neutral pH or acidic pH alone. These data suggest that alendronate stimulates net ion (Na) transport in esophageal epithelium by increasing apical membrane sodium channel activity and that this occurs with limited morphological change and no alteration in barrier function. Also alendronate is far more damaging at acidic than at neutral pH, suggesting its association with esophagitis requires gastric acid for expression. This expression may occur either by potentiation between the damaging effects of (refluxed) gastric acid and drug or by acid-induced conversion of the drug to a more toxic form.
 ...
PMID:Physiological and morphological effects of alendronate on rabbit esophageal epithelium. 1218 Nov 70

Epithelial cells in the kidney, gastrointestinal tract and exocrine glands are engaged in vectorial transport of salt and nutrients. In these tissues, K(+) channels play an important role for the stabilization of membrane voltage and maintenance of the driving force for electrogenic transport. Luminal K(+) channels represent an exit pathway for the excretion of K(+) in secreted fluid, urine and faeces, thereby effecting body K(+) homeostasis. Indeed, the expression and function of several luminal K(+) channels is modulated by hormones regulating water, Na(+), and K(+) metabolism. In addition to net transport of K(+) in the serosal (or apical) direction, K(+) channels can be coupled functionally to K(+)-transporting ATPases such as the basolateral Na(+)/K(+) ATPase or the luminal H(+)/K(+) ATPase. These ATPases export Na(+) or H(+) and take up K(+), which is then recycled via K(+) channels. This review gives a short overview on the molecular identity of epithelial K(+) channels and summarizes the different mechanisms of K(+) channel function during transport in epithelial cells.
 ...
PMID:Potassium channels in epithelial transport. 1270 75


<< Previous 1 2 3 4 5 6 Next >>