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)

We have compared the response of proton and water transport to oxytocin treatment in isolated frog skin and urinary bladder epithelia to provide further insights into the nature of water flow and H+ flux across individual apical and basolateral cell membranes. In isolated spontaneous sodium-transporting frog skin epithelia, lowering the pH of the apical solution from 7.4 to 6.4, 5.5, or 4.5 produced a fall in pHi in principal cells which was completely blocked by amiloride (50 microM), indicating that apical Na+ channels are permeable to protons. When sodium transport was blocked by amiloride, the H+ permeability of the apical membranes of principal cells was negligible but increased dramatically after treatment with antidiuretic hormone (ADH). In the latter condition, lowering the pH of the apical solution caused a voltage-dependent intracellular acidification, accompanied by membrane depolarization, and an increase in membrane conductance and transepithelial current. These effects were inhibited by adding Hg2+ (100 microM) or dicyclohexylcarbodiimide (DCCD, 10(-5) M) to the apical bath. Net titratable H+ flux across frog skin was increased from 30 +/- 8 to 115 +/- 18 neq.h-1.cm-2 (n = 8) after oxytocin treatment (at apical pH 5.5 and serosal pH 7.4) and was completely inhibited by DCCD (10(-5) M). The basolateral membranes of the principal cells in frog skin epithelium were found to be spontaneously permeable to H+ and passive electrogenic H+ transport across this membrane was not affected by oxytocin. Lowering the pH of the basolateral bathing solution (pHb) produced an intracellular acidification and membrane depolarization (and an increase in conductance when the normal dominant K+ conductance of this membrane was abolished by Ba2+ 1 mM). These effects of low pHb were blocked by micromolar concentrations of heavy metals (Zn2+, Ni2+, Co2+, Cd2+, and Hg2+). Lowering pHb in the presence of oxytocin (50 mU/ml) produced a transepithelial current (3 microA.cm-2 at pHb 5.5) which was blocked by 100 microM of Hg2+, Zn2+, or Ni2+ at the basolateral side, and by DCCD (10(-5) M) or Hg2+ (100 microM) from the apical side. The net hydroosmotic water flux (JH2O) induced by oxytocin in frog bladder sacs was blocked by inhibitors of H(+)-adenosine triphosphatase (ATPase). Diethylstilbestrol (DES 10(-5) M), oligomycin (10(-8) M), and DCCD (10(-5) M) prevented JH2O when present in the lumen. These effects cannot be attributed to inhibition of metabolism since cyanide (10(-4) M), or 2-deoxyglucose (10(-3) M) had no effect on JH2O.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Common channels for water and protons at apical and basolateral cell membranes of frog skin and urinary bladder epithelia. Effects of oxytocin, heavy metals, and inhibitors of H(+)-adenosine triphosphatase. 164 38

Recent studies indicate that in animals with marked cardiac hypertrophy, there is depressed function of Ca2+ sequestration by myocardial sarcoplasmic reticulum (SR) because of down regulation of the Ca(2+)-ATPase gene. However, in several animal models we have observed enhancement of myocardial Ca2+ sequestration in response to chronic cardiac stimulation. We tested the hypothesis that in animals with mild cardiac hypertrophy, there is enhanced Ca(2+)-cycling activity by the SR Ca2+ pump and Ca(2+)-release channel. Because creatine kinase activity is consistently decreased in cardiomyopathy, we also determined whether enhanced Ca2+ cycling was accompanied by down regulation or inhibition of the creatine kinase system. Mild cardiac hypertrophy was induced by volume overload; 2% salt was added to the diet of 2-week-old turkey poults for 4 weeks. Compared with age-matched controls, volume overload resulted in 14.3% increase in heart weight and 21.5% increase in heart-to-body weight ratios. The hypertrophied heart had approximately 20% increased activities of the SR Ca2+ pump and the SR Ca2+ channel. Net Ca2+ transport was increased by 16.5%. Compared with controls and in contrast to several other myocardial enzymes, creatine kinase activity was diminished in the hypertrophied hearts by 23% and creatine content was decreased by 8%. Differences between groups were not detected for lactate dehydrogenase, aspartate transaminase, and alanine transaminase. We concluded that an early adaptation of the myocardium undergoing hypertrophy in compensatory response to functional overload is an enhancement of Ca2+ cycling activity by the Ca2+ pump and Ca2+ channel of the SR.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effects of mild cardiac hypertrophy, induced by volume overload in turkeys, on myocardial sarcoplasmic reticulum calcium-pump and calcium-channel activities and on the creatine kinase system. 165 61

Net synthesis of the fast-type sarcoplasmic reticulum (SR) Ca2(+)-ATPase was studied in the muscle cell line L6AM using an immunochemical assay (e.l.i.s.a.). In addition, Ca2+ uptake by SR was monitored in muscle cell homogenates by a method employing the fluorescent Ca2+ indicator fura-2. Measurements were done both in differentiating myoblasts and in myotubes. Ca2(+)-ATPase levels were low (1 pmol/mg of protein) in undifferentiated myoblasts (controls) and only doubled over a period of 8 days in the absence of thyroid hormone (L-triiodothyronine; T3). This corresponded to a similar increase in Ca2+ uptake activity. Only half of the myoblasts fused under these conditions. Fusion was not increased in the presence of T3 (5 nM), but Ca2(+)-ATPase levels increased 4-fold and the Ca2+ uptake activity doubled compared with controls. In contrast, insulin-like growth factor-I (IGF-I) induced almost complete myotube formation (greater than 90% fusion), but only slightly stimulated (50%) net Ca2(+)-ATPase synthesis above control levels. However, the doubling of the Ca2+ uptake stimulation by IGF-I was comparable with that caused by T3. The effects of T3 plus IGF-I on Ca2(+)-ATPase levels and Ca2+ uptake activity were more than additive. Furthermore, the temporal relationship between the induction of Ca2(+)-ATPase net synthesis and Ca2+ uptake activity was identical with the two hormones. Qualitatively similar results were obtained when T3 and IGF-I were added to maximally fused cell cultures. The enhanced effect of T3 on Ca2(+)-ATPase net synthesis and Ca2+ uptake activity in the presence of IGF-I cannot therefore be explained by an increased myotube formation stimulated by the latter. In both differentiating myoblasts and myotubes the effect of T3 was more prominent on Ca2(+)-ATPase net synthesis than on Ca2+ uptake activity, whereas in myotubes the opposite was observed for IGF-I. This could imply complementary actions of the two agents in the development of a functional SR.
 ...
PMID:The elevation of sarcoplasmic reticulum Ca2(+)-ATPase levels by thyroid hormone in the L6 muscle cell line is potentiated by insulin-like growth factor-I. 182 34

In order to further test the validity of the vesicular transport model of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3)-stimulated intestinal calcium absorption, dose-response studies were undertaken. Using previously established methodology for subcellular fractionation following 45Ca absorption from in situ ligated duodenal loops, radionuclide levels were found to increase gradually in endocytic vesicles prepared from 1,25(OH)2D3-treated (+D) chicks relative to controls (-D) achieving a plateau at greater than or equal to 260 pmol seco-steroid. By comparison, lysosomal 45Ca levels increased more readily, having +D/-D ratios of 1.88 +/- 0.35, 2.21 +/- 0.05, 2.17 +/- 0.88, 2.31 +/- 0.25, and 2.15 +/- 0.47 after 0.0104, 0.052, 0.26, 1.3, or 6.5 nmol of 1,25(OH)2D3, respectively. Net intestinal calcium absorption, as judged by appearance of 45Ca in the serum for the same range of doses, rose gradually to a plateau value at greater than or equal to 260 pmol. Since lysosomal 45Ca levels were maximally increased at 1,25(OH)2D3 doses lower than those required for fully stimulated transport, it was concluded that lysosomes are still candidates for cellular calcium carriers, but that other elements of the transport pathway are required. Analyses of gradient fractions for calbindin-D28K (the vitamin D-induced calcium binding protein), and potential 1,25(OH)2D3-mediated changes in vesicular ATPase (microtubule motive power for transcellular delivery of calcium) failed to identify the missing components.
 ...
PMID:1,25-Dihydroxyvitamin D3-mediated vesicular calcium transport in intestine: dose-response studies. 253 14

Ca2+ transport by the inner medullary collecting duct (IMCD) of normal rats was studied using the "in vitro" microperfusion technique. Net (Jnet), lumen-to-bath (Jl----b), and bath-to-lumen (Jb----l) fluxes of Ca2+ were measured in the absence of net water absorption using 45Ca as a tracer. In the absence of an electrochemical gradient, an important net absorption of Ca2+ (11.1 +/- 1.6 pmol.cm-2.s-1), similar to the difference between the Jl----b and Jb----l, was observed by direct determination at low (5-6 nl/min) and high (12-17 nl/min) perfusion rates. The Jl----b of Ca2+ was reduced by the addition to the bath fluid of ouabain (10(-3) M) and verapamil (10(-4) M), by the presence of amiloride (10(-5) and 10(-3) M) and verapamil (10(-4) M) in the luminal fluid, or by perfusion with a Na+-free solution. Neither the presence of verapamil (10(-4) M) and ouabain (10(-3) M) in the bath nor the withdrawal of Na+ from bath and perfusion solution was able to modify the Jb----l of Ca2+. Incrementing Ca2+ bath concentration increased proportionally the Jb----l of Ca2+. Therefore Ca2+ outflux is in part dependent on Na+-K+-adenosinetriphosphatase luminal membrane Na+ transport and in part inhibited by verapamil. However, Ca2+ influx is independent of Na+ transport, is not blocked by verapamil, but is increased by Ca2+ transtubular gradient, indicating the presence of a passive diffusion mechanism.
 ...
PMID:Calcium transport across rat inner medullary collecting duct perfused in vitro. 258 80

We studied the effect of hydrochlorothiazide, 50 mg daily, on Na,K-adenosine triphosphatase (ATPase) activity in the red cells of 10 black men with hypertension. We also examined net sodium and potassium movement in sodium-loaded, potassium-depleted, red cells. Treatment with hydrochlorothiazide resulted in a significant increase in mean ouabain-sensitive ATPase activity (+/- SEM) from 118.4 +/- 14.6 to 158.1 +/- 15.3 nmol phosphate released per milligram of protein (P = 0.0004). Ouabain-resistant ATPase did not change. Net sodium extrusion rose significantly, from 1.62 +/- 0.27 to 2.32 +/- 0.33 mmol/L/hr (P = 0.0275). We postulate that the enhanced activity of the Na,K pump results from the volume contraction induced by the diuretic. This interpretation is consistent with the concept that the Na,K pump is inhibited in volume expansion and volume-expanded hypertension. The finding of enhanced pump activity in subjects given treatment with hydrochlorothiazide suggests a possible mechanism of the antihypertensive action of diuretic therapy.
 ...
PMID:Effect of treatment with hydrochlorothiazide on the red cell Na,K-adenosine triphosphatase in men with hypertension. 282 24

The effects of several natural products extracted from the leaves of Stevia rebaudiana on rat liver mitochondria were investigated. The compounds used were stevioside (a non-caloric sweetener), steviolbioside, isosteviol and steviol. Total aqueous extracts of the leaves were also investigated. S. rebaudiana natural products inhibited oxidative phosphorylation, ATPase activity NADH-oxidase activity, succinate-oxidase activity, succinate dehydrogenase, and L-glutamate dehydrogenase. The ADP/O ratio was decreased. Substrate respiration (state II respiration) was increased at low concentrations (up to 0.5 mM) and inhibited at higher concentrations (1 mM or more). In uncoupled mitochondria, inhibition of substrate respiration was the only effect observed. Net proton ejection induced by succinate and swelling induced by several substrates were inhibited. Of the compounds investigated, the sweet principle stevioside was less active. It was concluded that, in addition to the inhibitory effects, S. rebaudiana natural products may also act as uncouplers of oxidative phosphorylation. The possible physiologic consequences of the ingestion of stevioside and S. rebaudiana aqueous extracts are discussed.
 ...
PMID:Effects of Stevia rebaudiana natural products on rat liver mitochondria. 285 11

Electrolyte transport was studied in rat cecum and colon adapting to 60% resection of the small intestine. Four weeks after surgery, the absorbing gross surface area, dry and wet weight, net absorption in vivo of sodium, chloride and volume, net potassium secretion, transmural electrical potential difference and mucosal Na-K-ATPase specific activity were determined. In the cecum, all tissue mass parameters were increased compared to sham-operated controls. Net transport was stimulated per organ but not per unit mass, and potential difference and Na-K-ATPase remained unaffected. In the colon, surface area and wet weight increased slightly while dry weight and electrolyte transport were not influenced. Thus, by enlargement without a change in cell function, the cecum but not the colon contributes to electrolyte homoeostasis after 60% jejunoilectomy in the rat. Na-K-ATPase specific activity and electrical potential difference were higher in the colon than the cecum, suggesting segmental heterogeneity of the larger bowel with respect to Na-K-ATPase-linked active sodium absorption.
 ...
PMID:Adaptation of electrolyte transport in rat large intestine after proximal resection. I. Cecum and colon after 60% jejunoilectomy. 300 77

Electrolyte transport was studied in rat colon adapting to 50% small intestinal resection with cecectomy. Four weeks after surgery, colonic gross surface area, dry and wet weight were increased compared to sham-operated controls. Net absorption in vivo of sodium, chloride and volume was stimulated per organ and per unit tissue mass, and net potassium secretion was diminished. The electrical potential difference, mucosal Na-K-ATPase specific activity and cAMP concentration remained unaffected. In vitro, measurements of unidirectional fluxes and electrical parameters across isolated mucosa indicated enhanced electrically neutral sodium chloride absorption in the proximal and possibly diminished bicarbonate secretion in the distal colon. Thus, removal of the cecum in addition to partial jejunoilectomy induces profound adaptive changes in the colon, involving not only mucosal growth but also a functional reaction of the individual epithelial cell.
 ...
PMID:Adaptation of electrolyte transport in rat large intestine after proximal resection. II. Colon after 50% jejunoilectomy combined with cecectomy. 300 78

Inhibition of ADP phosphorylation by both glycolysis and mitochondria in P388D1 cells exposed to H2O2 is described. Net glucose uptake and lactate production were inhibited by oxidant exposure (ED50 = 50-100 microM). Glycolysis was specifically inactivated at the glyceraldehyde-3-phosphate dehydrogenase step by three independent mechanisms: (a) direct inactivation of the intracellular enzyme (ED50 approximately equal to 100 microM); (b) reduction of the intracellular concentration and redox potential of its nicotinamide cofactors; and (c) a cytosolic pH shift further from the enzyme optima. Consistent with inhibition of glycolysis at the glyceraldehyde-3-phosphate dehydrogenase step, a rise in the intracellular concentration of glyceraldehyde 3-phosphate, dihydroxyacetone phosphate, and fructose 1,6-bisphosphate was observed. The calculated combined inhibition of glyceraldehyde-3-phosphate dehydrogenase activity could be reasonably correlated with the depression in glycolytic flux rate with the appropriate modeling. The steady-state contribution by mitochondria to the total intracellular ATP pool was indirectly determined by the use of various metabolic inhibitors and was found to rapidly decline following exposure to 300-800 microM H2O2. The inhibition of ADP phosphorylation appeared to be related more to the direct inhibition of the ATPase-synthase complex rather than to the diminished capacity of the respiratory chain for coupled electron transport. Both the estimated rates of ADP phosphorylation by glycolysis and mitochondria and the estimated rate of ATP hydrolysis by ongoing metabolism were utilized to model the approximate decline in intracellular ATP expected at 15-min exposure to various H2O2 concentrations. Theoretical calculations and the measured intracellular ATP status were in good agreement. Oxidant exposure for 15 min resulted in dose-dependent killing of the cells (ED50 = 500 microM), indicating a close correlation between H2O2-mediated loss of intracellular ATP and cell viability. The possible contribution of impaired energy homeostasis during oxidant-mediated injury to the process of cell dysfunction and death is discussed.
 ...
PMID:Mechanisms of oxidant-mediated cell injury. The glycolytic and mitochondrial pathways of ADP phosphorylation are major intracellular targets inactivated by hydrogen peroxide. 333 86


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