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

Prostacyclin (PGI2) did not alter the basal perfusion pressure in the isolated rat mesenteric arteries perfused with Krebs' solution, but produced a biphasic effect in arteries preconstricted with norepinephrine or arginine vasopressin: constriction, then prolonged dilation. Both these components of PGI2 effect were diminished in arteries denuded of their endothelia by a 10 min perfusion with distilled water or p-bromophenacyl bromide (10 microM). The present study elucidates the mechanism of these PGI2 actions. Indomethacin (0.28 microM) SQ 29548 (1 microM, thromboxane A2 receptor antagonist), saralasin (1 microM, angiotensin II receptor antagonist) or the free radical scavengers, superoxide dismutase (60 U/ml) and catalase (40 U/ml) did not inhibit the initial vasoconstriction, suggesting it was not mediated through endothelially generated thromboxane A2, angiotensin II or oxygen-derived free radicals. However, ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid (50 microM; Ca++ chelating agent), 8-(diethyl-amino)octyl 3,4,5-trimethoxy benzoate (10 microM; intracellular Ca++ antagonist), or neomycin (5 mM; phospholipase-C inhibitor) abolished the vasoconstriction. Ouabain (0.5 mM) did not affect the vasodilation, but perfusion with excess (50 mM) or 0 K+ Krebs' solution abolished it, suggesting this PGI2 action involves changes in membrane K+ conductance via a mechanism independent of Na+/K+ adenosine triphosphatase. Vasodilation evoked by BRL 34915 (K+ channel activator) was similarly attenuated under these conditions, but not by ouabain. Furthermore, procaine (1 mM; nonspecific K+ channel inhibitor), but not apamin (0.5 microM) or tetraethylammonium (10 mM) blocked PGI2- and BRL 34915-induced vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism of vascular actions of prostacyclin in the rat isolated perfused mesenteric arteries. 210 93

1. The rates of translocation of oxaloacetate and l-malate into rat liver mitochondria were measured by a direct spectrophotometric assay. 2. Penetration obeyed Michaelis-Menten kinetics, and apparent K(m) values were 40mum for oxaloacetate and 0.13mm for l-malate. 3. Arrhenius plots of the temperature-dependence of rates of penetration gave activation energies of +10kcal./mole for oxaloacetate and +8kcal./mole for l-malate. 4. The translocation of both oxaloacetate and l-malate was competitively inhibited by d-malate, succinate, malonate, meso-tartrate, maleate and citraconate. The K(i) values of these inhibitors were similar for the penetration of both oxaloacetate and l-malate. 5. Rates of penetration were stimulated by NNN'N'-tetramethyl-p-phenylenediamine dihydrochloride plus ascorbate under aerobic conditions or by ATP under anaerobic conditions. 6. The energy-dependent stimulation of translocation was abolished by uncouplers of oxidative phosphorylation. Oligomycin A, aurovertin, octyl-guanidine and atractyloside prevented the stimulation by ATP, but did not inhibit the stimulation by NNN'N'-tetramethyl-p-phenylenediamine dihydrochloride plus ascorbate. 7. Mitochondria prepared in the presence of ethylene-dioxybis(ethyleneamino)tetra-acetic acid did not exhibit the energy-dependent translocation, but this could be restored by the addition of 50mum-calcium chloride. 8. Valinomycin or gramicidin plus potassium chloride enhanced the energy-dependent translocation of oxaloacetate and l-malate. 9. Addition of oxaloacetate stimulated the adenosine triphosphatase activity of the mitochondria, and the ratio of ;extra' oxaloacetate translocation to ;extra' adenosine triphosphatase activity was 1.6:1. 10. Possible mechanisms for the energy-dependent entry of oxaloacetate and l-malate into mitochondria are discussed in relation to the above results.
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PMID:Factors affecting the translocation of oxaloacetate and L-malate into rat liver mitochondria. 423 43

The in vivo anesthetic activity of monoketones in mice was examined in relation to their hydrophobicity and to the in vivo effects on Na+/K+ -adenosine triphosphatase (Na+/K+ -ATPase) activity and membrane fluidity. Anesthetic potency (AD50) of monoketones was determined; AD50 implys the dose required to anesthetize 50% of the animals from the treated group. The n-octanol/water partition coefficient (P) was used as an index of hydrophobicity. Membrane fluidity was determined by using 1,6-diphenyl-1,3,5-hexatriene (DPH) or 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH as fluorescence probes. Log (1/AD50) was the parabolic function of log P, log ((1/AD50) = -0.167(log P)2 + 0.698 log P - 1.365, and the log P that corresponds to the minimum AD50 was estimated to be 2.09. Brain synaptosomes were prepared from mice that were considered anesthetized with each of the 4 monoketones (1.5-fold AD50), methyl n-propyl, methyl n-amyl, methyl 3-methylhexyl and methyl n-octyl ketone. The Na+/K+ -ATPase activity was inhibited by methyl n-propyl ketone alone, membrane DPH fluidity was decreased by each of the 4 monoketones, and membrane TMA-DPH fluidity was decreased by methyl n-propylketone alone. These results suggest an involvement of the decreased DPH fluidity in monoketone-induced anesthesia.
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PMID:Anesthetic activity of monoketones in mice: relationship to hydrophobicity and in vivo effects on Na+/K+ -ATPase activity and membrane fluidity. 861 59