Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20020 (adenosine triphosphatase)
 3,299 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Transport of D-glucose, p-aminohippurate and tetraethylammonium has been studied using renal brush border membrane vesicles isolated from rats with uranyl nitrate-induced acute renal failure (ARF). Initial rate and overshoot magnitude of Na+ gradient-dependent D-glucose uptake were decreased in brush border membrane vesicles from ARF rats compared with normal rats, although there was no significant difference on D-glucose uptake in the presence of equilibrated Na+ between normal and ARF rats. Uptake of p-aminohippurate by membrane vesicles from ARF rats did not differ from normal membrane vesicles. Uptake of tetraethylammonium with or without an H+ gradient was decreased in membrane vesicles from ARF rats compared with normal rats. Dissipation rate of H+ gradient across brush border membranes did not differ between both groups. In vitro incubation of normal brush border membrane vesicles with uranyl nitrate caused no alteration in any substrate transport. However, enzyme activities such as (Na+ + K+)-adenosine triphosphatase in renal cortical homogenate were inhibited markedly in the presence of uranyl nitrate. These results suggest that uranyl nitrate-induced ARF caused alterations in the transport properties of renal brush border membranes and that these transport dysfunctions were not due to the direct effect of uranyl nitrate, but could be secondarily induced after the impairment of the integrity for tubular cells.
 ...
PMID:Transport of p-aminohippurate, tetraethylammonium and D-glucose in renal brush border membranes from rats with acute renal failure. 298 96

Nervous or hormonal stimulation of salivary secretion in vivo is associated with a pronounced efflux of K+ from the secretory, acinar cells into the blood. This K+ efflux is followed in the post-stimulus period by a reuptake of K+ into the glandular tissue. In the present study we monitor the changes in [K+] of physiological solutions perfusing a flow chamber containing isolated segments of mouse submandibular glands. Nervous stimulation or the application of exogenous acetylcholine (ACh, 10(-5) M) to the isolated glandular tissue results in characteristic changes in the [K+] of the superfusate, indicating net K+ release followed by K+ reuptake. The post-stimulus reuptake of K+ is shown to be susceptible to blockade by either ouabain (10(-3) M) or piretanide (10(-4) M). The reuptake was markedly attenuated if Cl- in the superfusate was replaced by either NO3- or SO4(2-). The K+ uptake was, however, unaffected when Br- replaced Cl- in the superfusate. Similar effects were observed in the unstimulated glandular tissues. The introduction of Cl-(-)free media containing either NO3- or SO4(2-) resulted in a loss of K+ from the tissue which was followed, upon reintroduction of Cl-, by a pronounced uptake of K+. When Br- was substituted for Cl- there was very little change in [K+] upon removal or reintroduction of Cl-. The uptake of K+ induced by reintroduction of Cl- after a period of NO3- or SO4(2-) superfusion was blocked by both ouabain and piretanide. This uptake of K+ was also dependent on the presence of extracellular Na+. Both Cl- and Na+ had to be present in the superfusing medium for K+ uptake to be fully manifest. These findings indicate that the K+ uptake observed in both the resting and stimulated submandibular gland cannot be explained as solely due to the activity of the Na+-K+-adenosine triphosphatase (Na+-K+-ATPase). The demonstrated anionic selectivity, dependence on extracellular Na+ and susceptibility to blockade by the diuretic piretanide would strongly suggest that a coupled Na+-K+-Cl- co-transport system operates in submandibular glands as it does in other transporting epithelia to achieve K+ uptake.
 ...
PMID:Potassium uptake in the mouse submandibular gland is dependent on chloride and sodium and abolished by piretanide. 379 14

A major research program in the University of Maryland School of Medicine, Department of Pharmacology, in the 1930s was the preparation of a large number of sugar alcohols and their anhydrides as substitute carbohydrates for diabetic diets. As an outgrowth of this work, many of these polyols were converted to their nitrate esters and investigated for their vasodilating properties. The organic nitrates that were synthesized were examined for their potency, duration of action, and possible therapeutic use. It was demonstrated that, contrary to prior belief, the depressor and vasodilating action was exhibited by their own molecular structure and not through hydrolysis and reduction to nitrite. The search for the finer mechanism(s) of action on the vascular musculature showed that these nitrated polyols and their anhydrides inhibited arterial adenosine triphosphatase, although this enzyme inhibition did not correlate with pharmacologic activity. Today the mechanism of action of these drugs is not clearly understood at the cellular level. The 1,4:3,6-dianhydrosorbitol 2,5-dinitrate (isosorbide dinitrate) was synthesized, studied, and reported in 1940. It appeared to be a useful drug because blood levels of the unhydrolyzed ester were found to persist for long periods of time. Subsequent clinical studies in the 1960s demonstrated its prophylactic value in angina pectoris and its prolonged action as a therapeutic asset. In 1967 the mononitrate was shown to be formed in vivo when the dinitrate was administered orally and has been studied as the possible pharmacodynamically active moiety.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:History of the synthesis and pharmacology of isosorbide dinitrate. 389 78

1. ATP sulphurylases were partially purified (20-40-fold) from leaf tissue of Astragalus bisulcatus, Astragalus racemosus (selenium-accumulator species) and Astragalus hamosus and Astragalus sinicus (non-accumulator species). Activity was measured by sulphate-dependent PP(i)-ATP exchange. The enzymes were separated from pyrophosphatase and adenosine triphosphatase activities. The properties of the Astragalus ATP sulphurylases were similar to the spinach enzyme. 2. The ATP sulphurylases from both selenium-accumulator and non-accumulator species catalysed selenate-dependent PP(i)-ATP exchange; selenate competed with sulphate. The ratio of V(selenate)/V(sulphate) and K(m)(selenate)/K(m)(sulphate) was approximately the same for the enzyme from each species. 3. Sulphate-dependent PP(i)-ATP exchange was inhibited by ADP, chlorate and nitrate. The kinetics of the inhibition for each enzyme were consistent with an ordered reaction mechanism, in which ATP is the first substrate to react with the enzyme and PP(i) is the first product released. 4. Synthesis of adenosine 5'-[(35)S]sulphatophosphate from [(35)S]sulphate was demonstrated by coupling the Astragalus ATP sulphurylases with Mg(2+)-dependent pyrophosphatase; the reaction was inhibited by selenate. An analogous reaction using [(75)Se]selenate as substrate could not be demonstrated.
 ...
PMID:Comparative enzymology of the adenosine triphosphate sulphurylases from leaf tissue of selenium-accumulator and non-accumulator plants. 437 98

The ultrastructure of bony-fish heart tissue is described when subjected to beta-glycerophosphate/lead citrate (9.2 less than or equal to pH less than or equal to 9.4) or adenosine triphosphate/lead nitrate (pH = 7.3). When treated in the former way, electron dense precipitates occur in the endocardial and myocardial endoplasmic/sarcoplasmic reticulum, Golgi apparatus, and nuclear intermembranous space. Such precipitates are absent in the control tissue and reflect therefore probably alkaline phosphatase activity. In tissue treated with adenosine triphosphate/lead nitrate the precipitates are irregularly distributed, and may also occur in the control tissue. In the present material, they therefore seem not to reflect adenosine triphosphatase activity. The results are compared and discussed with those revealed in the present study for the bony-fish intestine and with those previously reported for various mammalian tissues.
 ...
PMID:Ultrastructure of bony-fish heart tissue treated with beta-glycerophosphate/lead citrate or adenosine triphosphate/lead nitrate. 608 87

Discrete sites of adenosine triphosphatase (ATPase) activity were demonstrated within the nucleoli of unfixed cultured human fibroblasts (IMR90, VA13, and AG2804 cells) by an adaptation, for electron microscopic cyto-chemistry, of Wachstein and Meisel's lead nitrate method. The majority of nucleoli contained more than one ATPase-positive region, but the total ATPase-positive material appeared to occupy only a minor portion of the nucleolar volume. These regions were roughly spherical with an irregular contour, and at times appeared to be components of perinucleolar chromatin or to be located adjacent to nucleolar interstices. The distribution of these regions within the nucleolus and their segregation by actinomycin D suggested that the ATPase-positive regions correspond to the fibrillar centers, which represent nucleolar organizer regions. The cytochemically demonstrable nucleolar ATPase was strictly dependent on the presence of divalent cations. Optimal reactions was seen at 5 mM Mg2+, but near optimal activity was obtained with lower concentrations of Mg2+ in the presence of Ca2+. Calcium alone and Mn2+ alone produced suboptimal reaction. Studies with different nucleoside phosphates as reaction substrates showed that the enzyme is specific for adenosine derivatives, ATP and dATP being equally good substrates. Guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and d-thymidine triphosphate were ineffective as substrates, as were nucleoside mono- and diphosphates and other phosphate esters tested. It is suggested that the cytochemical ATPase reaction visualized the regions of the nucleolus in which ribosomal DNA of intranucleolar chromatin is undergoing conformational alterations.
 ...
PMID:Visualization of nucleolar substructure in cultured human fibroblasts by magnesium-activated adenosine triphosphatase reaction. 611 91

Inhibition of adenosine triphosphatase (ATPase) by silver nitrate (AgNO3) in vitro was studied in microsomal fractions or tissue homogenates of canine brain and kidney, and human kidney. In microsomal fractions, AgNO3 was an indiscriminate inhibitor of ouabain-sensitive (Na+ + K+ ATPase) and ouabain-insensitive (Mg2+ ATPase) activities with 50% inhibition obtaining at concentrations on the order of 10(-7) to 10(-6)M. The enzyme was protected by cysteine. Changing the concentrations of Na+, K+, H+, Mg2+ and ATP did not alter the fractional inhibition of Na+ + K+ ATPase by a constant concentration of AgNO3. An aqueous suspension of silver sulfadiazine had an inhibitory potency similar to AgNO3. It was concluded that silver gives a different pattern of Na+ + K+ ATPase inhibition than other metallic inhibitors of the enzyme so far examined.
 ...
PMID:Inhibition of adenosine triphosphatase in vitro by silver nitrate and silver sulfadiazine. 624 May 33

The responses of the cytosolic pH of hepatocytes in suspension to agents affecting the activity of vacuolar adenosine triphosphatase (V-ATPase) and Na/H exchange have been studied. Changes of cytosolic pH were determined both with dual-wavelength excitation (500/440 nm) of the fluorescence of 2',7'-bis-(2-carboxyethyl)-5(and 6)-carboxyfluorescein and from the distribution of 14C-dimethyloxazolidinedione; both methods gave very similar results. Changes of vesicular pH were determined by comparing the fluorescence of fluorescein isothiocyanate-dextran and rhodamine B isothiocyanate-dextran taken up by endocytosis. Nitrate, which inhibits V-ATPase in isolated organelles, induced a concentration-dependent acidification of the cytosol and alkalinization of vesicles, with maximal effects at 25-37.5 mM in each case, indicating that V-ATPase contributes to removal of cytosolic protons. On continued exposure to nitrate, the acidification underwent an amiloride-inhibitable reversal. At the higher concentrations of NO3-, both cytosolic acidification and vesicular alkalinization were reduced or absent. Bafilomycin A1 caused alkalinization of vesicular pH; cytosolic acidification was not observed, possibly because of other ionic exchanges. Recovery of cytosolic pH from an acid load (2 min exposure to 5% CO2) was sensitive to both 25 mM NO3- and to ouabain. The pH dependence of the nitrate effect was tested with media of different pH; the activity was negligible at cytosolic pH 6.2 and rose to a maximum at cytosolic pH 7.3. Treatment of hepatocytes with 0.5-1.0 mM ouabain resulted in an initial alkalinization (0.5-2 min duration) of the cytosol, followed by a spontaneous reversal and, on occasion, further acidification. The alkalinization was blocked by 25 mM NO3-, but not by 25 mM gluconate. The results suggest that the cytosolic alkalinization is caused by a stimulation of H+ uptake by V-ATPase activity. We conclude that V-ATPase make an important contribution to the regulation of the cytosolic pH of hepatocytes.
 ...
PMID:Role of vacuolar adenosine triphosphatase in the regulation of cytosolic pH in hepatocytes. 770 51

The effects of two chelating agents, meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane 1-sulfonate (DMPS) on the mobilization, distribution, hepatic and hematopoietic toxicity of beryllium were compared in male rats exposed to beryllium. Animals were exposed to beryllium nitrate (0.5 mg/kg, orally, daily 5 days/week) for 21 days. Twenty-four hours after the last dose they were injected with a chelating agent (DMSA or DMPS) (25 or 50 mg/kg, twice daily for 5 days). The administration of DMSA and DMPS at a dose of 50 mg/kg marginally elevated the fecal excretion of beryllium. DMPS was effective in depleting beryllium from the liver, spleen and kidneys. However, DMPS (50 mg/kg) results in the redistribution of beryllium to blood. Beryllium-induced inhibition of hepatic alkaline phosphatase and hepatic adenosine triphosphatase (ATPase) were restored considerably with the chelating agents. Also, hepatic and renal histopathological lesions were less marked in rats treated with DMPS (50 mg/kg) compared with those treated with beryllium per se and DMSA. These effects were more prominent at the 50-mg/kg dose of chelating agents than at 25 mg/kg. These results suggest that treatment with DMPS has some beneficial effects in experimental beryllium intoxication.
 ...
PMID:Effects of meso-2,3-dimercaptosuccinic acid or 2,3-dimercaptopropane 1-sulfonate on beryllium-induced biochemical alterations and metal concentration in male rats. 782 83

Nitrated gitoxins (4) and bufotoxin homologues with various lengths of alkyl chain at C-3 of the steroid nucleus (10) were prepared from gitoxin (1). The pharmacological activities of the resulting compounds (4 and 10) were evaluated by measurement of inhibitory effect on NA+, K(+)-adenosine triphosphatase (ATPase) prepared from dog kidney, positive inotropic effect (PIE) on isolated guinea-pig papillary muscle preparations, and the effect on smooth muscle using the mesenteric artery from spontaneously hypertensive rats. Most of the compounds showed a smaller contractile effect on the arterial muscle. Among these compounds, gitoxin 3"-nitrate (4g) exhibited the most desirable biological activities, such as PIE comparable to that of 1, 1.25 times wider concentration-dependent range than 1, and lack of contractile activity on vascular muscle.
 ...
PMID:Studies on cardiac ingredients of plants. XIII: Chemical modification of gitoxin to cardiotonic compounds without vascular effect. 914 99


<< Previous 1 2 3 Next >>