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)

K+- and ATP-dependent H+-accumulation in rat heavy gastric membrane vesicles enriched with (H+-K+)-ATPase was markedly stimulated by amphiphiles like lysophosphatidylcholine and Zwittergent 3-14 at concentrations of 10(-5) M. Their stimulatory effect was dependent on K+-concentration in the medium and was abolished by SCH 28,080, a specific inhibitor of (H+-K+)-ATPase. Lysophosphatidylcholine at the optimal dose (3 X 10(-5) M) showed dual effects on K+-dependent membrane functions; it stimulated the rate of K+-uptake by nearly 60%, but partially inhibited SCH 28,080-sensitive and K+-dependent ATP-hydrolysis (about 20% reduction). These data indicate that H+-pumping through (H+-K+)-ATPase in the inside-out gastric membrane vesicles was facilitated by the stimulatory effect of lysophosphatidylcholine on membrane K+-transport in spite of its partial inhibition of ATP-hydrolysis. It appears that the rate limiting step for operation of the ATPase is the availability of K+ ions in the luminal side of the pump. We propose that ionic amphiphiles may modulate K+-transport in rat heavy gastric membranes through specific interactions with the putative K+-transporter.
 ...
PMID:Effect of lysophosphatidylcholine on K+ transport in rat heavy gastric membranes enriched with (H+-K+)-ATPase. 288 67

A photoaffinity label for the lumenal K+ site of the gastric (H+ + K+)-ATPase has been identified. Seven azido derivatives based upon the reversible K+ site inhibitor SCH 28080 were studied, one of which, m-ATIP (8-(3-azidophenylmethoxy)-1,2,3-trimethylimidazo[1,2-a] pyridinium iodide), was subsequently synthesized in radiolabeled form. In the absence of UV irradiation, m-ATIP inhibited K+ -stimulated ATPase activity in lyophilized gastric vesicles competitively with respect to K+, with a Ki value of 2.4 microM at pH 7.0. Irradiation of lyophilized gastric vesicles at pH 7.0 with [14C]m-ATIP in the presence of 0.2 mM ATP resulted in a time-dependent inactivation of ATPase activity that was associated with an incorporation of radioactivity into a 100-kDa polypeptide representing the catalytic subunit of the (H+ + K+)-ATPase. Both inactivation and incorporation were blocked in the presence of 10 mM KCl but not with 10 mM NaCl, consistent with interaction at the K+ site. The level of incorporation required to produce complete inhibition of ATPase activity was 1.9 +/- 0.2 times the number of catalytic phosphorylation sites in the same preparation. Tryptic digestion of gastric vesicle membranes, labeled with [14C]m-ATIP, failed to release the radioactivity from the membranes suggesting that the site of interaction was close to or within the membrane-spanning sections of this ion pump.
 ...
PMID:Photoaffinity labeling of the lumenal K+ site of the gastric (H+ + K+)-ATPase. 292 19

An electrogenic H-ATpase sensitive to inhibition by N-ethyl-maleimide has been reported to be present in renal distal tubules. In contrast to another H-ATPase (gastric H-K-ATPase), the renal enzyme is not stimulated by K+ and is not inhibited by vanadate. However, our preliminary observations indicated that a K-stimulated ATPase (K-ATPase) sensitive to inhibition by vanadate is present in renal medullary collecting duct (MCD). To localize and further characterize this renal tubular K-ATPase, we measured K-ATPase activity in eight specific segments of the rabbit nephron. K-ATPase activity was the difference in ATPase activity in the presence and absence of KCl but in the presence of ouabain (to inhibit Na-K-ATPase). ATPase activity was determined by a fluorometric microassay in which ATP hydrolysis is coupled to the oxidation of NADH. There was a significant K-ATPase activity (expressed as pmol.min-1.mm-1) in the connecting tubule (CNT, 17.0 +/- 3.3), cortical collecting duct (CCD, 6.6 +/- 0.7), and MCD (8.8 +/- 1.7), but not in the proximal segments and the thick ascending limbs. The renal tubular K-ATPase was not only inhibited by vanadate but also by omeprazole and SCH 28080 (relatively specific inhibitors of gastric H-K-ATPase). It is concluded that K-ATPase present in the CNT, CCD, and MCD has some properties in common with gastric H-K-ATPase. However, the physiological role of K-ATPase in the distal nephron segments remains to be elucidated.
 ...
PMID:Ouabain-insensitive K-adenosine triphosphatase in distal nephron segments of the rabbit. 296 63

The novel antiulcer agents, SCH 28080 and SCH 32651 were examined for their ability to inhibit the H+K+ ATPase enzyme activity in a preparation of microsomal membranes from rabbit fundic mucosa. SCH 28080 inhibited the isolated enzyme activity with a potency similar to omeprazole, IC50s of 2.5 and 4.0 microM respectively. SCH 32651 was less potent exhibiting an IC50 of 200.0 microM. Both compounds may therefore exert their antisecretory activity via a direct inhibition of the parietal cell H+K+ ATPase.
 ...
PMID:Inhibition of H+K+ATPase by SCH 28080 and SCH 32651. 299 1

The mechanism of the gastric antisecretory action of SCH 28080 has been studied utilizing two different in vitro test systems, isolated and enriched parietal cells from the guinea-pig and guinea-pig gastric membranes purified and enriched with K+/H+-ATPase. In guinea-pig isolated and enriched parietal cells SCH 28080 inhibited the acid response to histamine and high K+ concentrations with IC50 values not significantly different from each other. SCH 28080 inhibited the purified K+/H+-ATPase measured in the presence of 5 mM KCl with an IC50 value of 1.3 microM. Kinetic studies indicated a competitive inhibition of ATPase by SCH 28080 with respect to K+. Studies on Na+/K+-ATPase showed that this enzyme was only slightly depressed by SCH 28080. It is concluded that SCH 28080 acts with high selectivity on the parietal cell K%/H+-ATPase, establishing its antisecretory effect by a competitive interaction with the high affinity K+-site of the gastric ATPase.
 ...
PMID:Mechanism of gastric antisecretory effect of SCH 28080. 301 Nov 71

The novel antisecretory agents SCH 32651 and SCH 28080 were evaluated for their antisecretory activities in vitro as well as for their abilities to inhibit the (H+ + K+)-ATPase enzyme activity in preparations of microsomal membranes from rabbit fundic mucosa. SCH 32651 and SCH 28080 inhibited both the histamine- and dibutyryl cAMP-stimulated uptake of [14C]-aminopyrine into isolated parietal cells with IC50 values of about 1.5 and 0.02 microM respectively. SCH 32651 and SCH 28080 competitively inhibited the K+-stimulated hydrolysis of ATP catalyzed by the (H+ + K+)-ATPase with Ki values of 16.3 and 0.12 microM respectively. The inhibition of the enzyme by both compounds was not affected by the addition of the sulfhydryl reducing agents dithiothreitol or beta-mercaptoethanol, was readily reversible by dilution or washing, and was dependent upon the concentration of KCl used to stimulate the enzyme. These data suggest that SCH 32651 and SCH 28080 are reversible, competitive inhibitors of the K+-stimulated hydrolysis of ATP.
 ...
PMID:Studies on the mechanism of action of the gastric microsomal (H+ + K+)-ATPase inhibitors SCH 32651 and SCH 28080. 302 7

A novel class of antiulcer agents, the substituted imidazo[1,2-a]pyridines, is described. The present compounds are not histamine (H2) receptor antagonists nor are they prostaglandin analogues, yet they exhibit both gastric antisecretory and cytoprotective properties. The mechanism of gastric antisecretory activity may involve inhibition of the H+/K+-ATPase enzyme. Structure-activity studies led to the identification of 3-(cyanomethyl)-2-methyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine, SCH 28080 (27), which was selected for further development and clinical evaluation.
 ...
PMID:Antiulcer agents. 1. Gastric antisecretory and cytoprotective properties of substituted imidazo[1,2-a]pyridines. 400 11

Effects of SCH 32651, a novel antisecretory and cytoprotective agent, on resting and stimulated acid secretion by the guinea-pig isolated fundic mucosa were studied. SCH 32651 inhibited resting acid secretion in proportion to concentrations in serosal solution (0.1-10 microM), the IC50 being 4.4 microM. Cimetidine and atropine at concentrations up to 100 microM were inactive. Serosal application of SCH 32651 inhibited acid secretory responses to histamine (10 microM), methacholine (1 microM) or dibutyryl cyclic AMP (0.5 mM) plus theophylline (1 mM) in a concentration-dependent manner. The IC50S against histamine, methacholine and db cyclic AMP plus theophylline were 4.2 microM, 0.71 microM and 2.9 microM, respectively. In contrast, atropine and cimetidine each at 100 microM, a concentration that entirely abolished responses to methacholine and histamine, respectively, did not affect acid responses to db cyclic AMP plus theophylline. The inhibitory effects of SCH 32651 on resting and histamine-stimulated acid secretion were readily reversible upon washing. SCH 32651 0.1 mM in the mucosal solution also greatly suppressed the resting and stimulated acid secretion. In the presence of histamine treatment, SCH 32651 concomitantly caused a marked rise in K+ entry into the mucosal solution in parallel to a decline in the appearance of H+ in the same solution. The various events demonstrated by SCH 32651 in the present study are shared by omeprazole, a potent antisecretory agent working through inhibition of gastric H+/K+-ATPase. We conclude that SCH 32651 as a potent antisecretory agent seems to act directly on the parietal cell, near or at the site of H+/K+-ATPase which is a final step in the acid secretory process triggered by various stimuli.
 ...
PMID:Effects of SCH 32651 on resting and stimulated acid secretion in guinea-pig isolated fundic mucosa. 609 29

The cDNA for ATP1AL1, the fifth member of the human Na-K-adenosinetriphosphatase (ATPase)/H-K-ATPase gene family, was recently cloned (A. V. Grishin, V. E. Sverdlov, M. B. Kostina, and N. N. Modyanov. FEBS Lett. 349: 144-150, 1994). The encoded protein (ATP1AL1) has all the primary structural features common to the catalytic alpha-subunit of ion-transporting P-type ATPases and is similar (63-64% identity) to the Na-K-ATPase alpha-subunit isoforms and the gastric H-K-ATPase alpha-subunit. In this study, ATP1AL1 was expressed in Xenopus laevis oocytes in combination with the beta-subunit of rabbit gastric H-K-ATPase. The functional properties of the stable alpha/beta-complex were studied by 86Rb+ uptake and demonstrated that ATP1AL1 is a novel human K(+)-dependent ATPase [apparent half-constant activation/(K1/2) for K+ approximately 375 microM)]. ATP1AL1-mediated inward K+ transport was inhibited by ouabain (inhibition constant approximately 13 microM) and was found to be inhibited by high concentrations of SCH-28080 (approximately 70% at 500 microM). ATP1AL1 expression resulted in the alkalinization of the oocytes' cytoplasm and ouabain-sensitive proton extrusion, as measured with pH-sensitive microelectrodes. These data argue that ATP1AL1 is the catalytic alpha-subunit of a human nongastric P-type ATPase capable of exchanging extracellular potassium for intracellular protons.
 ...
PMID:Human ATP1AL1 gene encodes a ouabain-sensitive H-K-ATPase. 748 70

When current was sent from serosa (S) to mucosa (M) across the frog stomach, there was a polarization (POL) of the open circuit potential (OCPD). POL was not affected by NaCl-free solutions, but was decreased by inhibitors of the H+ pump. In present experiments, current was sent to clamp the PD (VC) across the mucosa in steps of 20 mV up to 100 mV below the control OCPD, that is, current was sent from M to S. All experiments were performed in NaCl-free solutions. The POL was expressed as a % of the difference between the VC PD and the control OCPD. In 4 mM K+ control solutions, the POL was 11.8%; with 10(-3) M omeprazole (H+/K+ pump inhibitor), 1.1; with 10(-5) M SCH 28080 (H+/K+ pump inhibitor), 3.6; with 10(-3) M famotidine (H2 blocker), 1.6; and with 10(-2) M SCN-, 25.4 (inhibition of H+ sec, but not of the pump); in 79 mM K+ control solutions, 26.2; with 10(-3) M omeprazole, 4.2; with 10(-5) M SCH 28080, 15.9; with 10(-3) M famotidine, 5.6; and with 10(-2) M SCN-, 29.9. POL was higher in high K+ than in low K+ solutions contrary to what was observed in previous experiments with current sent from S to M. Results are explained on the basis of an electrogenic H+/K(+)-ATPase pump which includes a H+ channel, permeable to K+. With high K+ solutions, K+ is driven through the H+ channel onto the antiporter (ATPase) when current is sent from M to S, resulting in a greater POL of the pump.
 ...
PMID:Effect of current direction and K+ on polarization of the frog gastric mucosa proton pump. 749 46


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