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)

Recently, we have shown that a hydrophobic amine (AU-1421) produces an irreversible inactivation of Na+/K(+)-ATPase activity. This inactivation was prevented by K+ and its congeners. In this study, we examined the possibility of Ca2+ or ethylenediamine as a probe of the K+ occlusion center of Na+/K(+)-ATPase. The inactivation by AU-1421 was prevented by Ca2+ with an apparent high affinity (approximately 0.1 mM). Ca2+ protection was cancelled by high concentrations of ATP, ADP or Mg2+. Ca2+ and K+ were similar in these respects. Kinetic analyses of the above data indicated the presence of two AU-1421 occlusion sites on the enzyme, either one of which is susceptible to Ca2+ occlusion. Ethylenediamine also prevented the inactivation by AU-1421 or by C12E8 solubilization of the enzyme, suggesting that ethylenediamine, like K+, stabilized the enzyme. However, an apparent affinity of ethylenediamine (approximately 1.4 mM) was one order of magnitude lower than that of K+ (approximately 0.2 mM), and the protective manner did not show a simple competition. In addition, ethylenediamine binding was unaffected by ATP or ADP at a low affinity site, and antagonized K+ binding. From these results we concluded that ethylenediamine does not act like K+ or Ca2+ in protecting AU-1421 inactivation, since it can't stabilize the enzyme conformation as an E2 (K(+)-bound form).
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PMID:(Z)-5-methyl-2-[2-(1-naphthyl)ethenyl]-4-piperidinopyridine (AU-1421), calcium ions and ethylenediamine as the K(+)-site directed probe for Na+/K(+)-ATPase. 217 5

(1) Ethylenediamine is an inhibitor of Na+- and K+-activated processes of Na+/K+-ATPase, i.e. the overall Na+/K+-ATPase activity, Na+-activated ATPase and K+-activated phosphatase activity, the Na+-activated phosphorylation and the Na+-free (amino-buffer associated) phosphorylation. (2) The I50 values (I50 is the concentration of inhibitor that half-maximally inhibits) increase with the concentration of the activating cations and the half-maximally activating cation concentrations (Km values) increase with the inhibitor concentration. (3) Ethylenediamine is competitive with Na+ in Na+-activated phosphorylation and with the amino-buffer (triallylamine) in Na+-free phosphorylation. Significant, though probably indirect, effects can also be noted on the affinity for Mg2+ and ATP, but these cannot account for the inhibition. (4) Inhibition parallels the dual protonated or positively charged ethylenediamine concentration (charge distance 3.7 A). (5) Direct investigation of interaction with activating cations (Na+, K+, Mg+, triallylamine) has been made via binding studies. All these cations drive ethylenediamine from the enzyme, but K+ and Mg+ with the highest efficiency and specificity. Ethylenediamine binding is ouabain-insensitive, however. (6) Ethylenediamine neither inhibits the transition to the phosphorylation enzyme conformation, nor does it affect the rate of dephosphorylation. Hence, we provisionally conclude that ethylenediamine inhibits the phosphoryl transfer between the ATP binding and phosphorylation site through occupation of cation activation sites, which are 3-4 A apart.
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PMID:Ethylenediamine as active site probe for Na+/K+-ATPase. 254 70

Inhibition of renin secretion from incubations of rat kidney cortex by angiotensin II (AII), ouabain and K+ depletion, depended on the presence of external Ca2+. AII inhibition of isoprenaline-stimulated renin secretion was only partially dependent on external Ca2+. Ouabain and K+ depletion inhibited isoprenaline-stimulated renin release but only in the presence of external Ca2+. Since, in Ca2+-free medium, isoprenaline stimulated renin release when the Na+/K+-ATPase was blocked, isoprenaline probably does not act through the Na+/K+-ATPase. Lanthanum blocked the stimulation of renin release by isoprenaline. Ethylenediamine tetra-acetic acid (EDTA) and ethyleneglycol-bis-(beta-amino-ethyl ether) N,N'-tetra-acetic acid (EGTA) increased renin secretion to a similar degree in Ca2+- and Mg2+-free buffer. When Mg2+ was present the effect of EGTA, but not EDTA, was considerably reduced. Verapamil reduced the fall in basal renin secretion in normal but not Ca2+-free buffer. Verapamil did not block the inhibitory effects of AII or ouabain and did not alter the stimulation of renin secretion by isoprenaline. Bay K 8644 inhibited renin secretion from cortex incubated in medium containing 15 mM K+ and this was dependent on extracellular Ca2+. In normal buffer (5.9 mM K+) Bay K 8644 increased renin secretion.
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PMID:Stimulation and suppression of renin release from incubations of rat renal cortex by factors affecting calcium flux. 354 5