Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While the stimulatory effect of vanadate, an anion of pentavalent vanadium, on adenylate cyclase (AC) has been repeatedly demonstrated in various tissues only a few studies have been hitherto devoted to the effect of vanadyl, a cation of tetravalent vanadium, but these have provided contradictory results. In the present experiments synaptic plasma membranes from normal rat cerebral cortex were used for estimation of the vanadyl effect (in the concentration range from 10(-5) mol.1(-1) to 10(-3) mol.1(-1) on the basal adenylate cyclase activity. Four types of incubation media were used. In the presence of Tris-maleate and creatine phosphate + creatine phosphokinase (CP + CK) maximal stimulation (33%) was reached at 10(-4) mol.1(-1). In the same buffer but in absence or (CP + CK) maximum was already obtained at 10(-5) mol.1(-1) (49%); at 10(-3) mol.1(-1) no effect was observed. In Tric.HCl buffer with (CP + CK) maximal stimulation appeared at 10(-5) mol.1(-1), whereas at 10(-3) mol.1(-1) inhibition (-25%) was observed. In a medium containing Tris.HCl without (CP + CK) the biphasic nature of vanadyl effect was less markedly expressed: maximal stimulation (+55%) occurred at 10(-4) mol.1(-1). Thus vanadyl stimulates AC, but at relatively low concentrations (10(-5)-10(-4); at higher concentration it tends to exert an inhibitory action. Vanadate had a qualitatively similar effect, but the stimulation was more pronounced and the tendency to inhibition was shifted to higher concentrations.
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PMID:Does vanadyl affect adenylate cyclase? 297 14

We have studied the effect of vanadium on steroidogenesis using dispersed cells from rat adrenals. It was found that when the cells were stimulated by ACTH both vanadate and vanadyl sulfate inhibited adrenal steroidogenesis. In contrast, when steroidogenesis was supported by cAMP analogues, no inhibition was observed. The inhibitory action of vanadium compounds was also seen when cholera toxin or forskolin was used as a stimulant instead of ACTH, indicating that vanadate does not act on the ACTH-receptor protein. When adrenal cells were stimulated by ACTH, cholera toxin- or forskolin-supported cAMP levels were diminished equally by vanadate. In addition, the mitochondrial steroid hydroxylation per se was not inhibited by vanadium compounds using either endogenous or exogenous steroid substrates. Based on these results, it is concluded that the site of inhibition by vanadium is located in the vicinity of the guanine nucleotide-binding protein and the catalytic unit of adenylate cyclase.
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PMID:Vanadium inhibits ACTH-mediated but not cyclic AMP-dependent adrenal steroidogenesis. 300 81

Vanadate(V), which has positive inotropic, natriuretic and vasoconstrictive effects, is taken up by cardiac cells and erythrocytes in large quantities. Most of the intracellular vanadium is shown to exist as protein-bound vanadyl(IV), however Vanadate (VO3) is a powerful inhibitor of the (Na+ rK+)-ATPase and the Ca++-ATPase, whereas it stimulates adenylate cyclase of cardiac tissue. Vanadyl (VO2+) has no or much less effects on these enzymes. Plasma membranes of cardiac tissue (cat, calf, human) as well as erythrocytes contain an enzyme that converts vanadate(V) to vanadyl(IV) in the presence of NADH but not NADPH. The optimal conditions for this NADH-vanadate-oxidoreductase are: pH 6.8, 1 mM, NADH, 1.5 mM Va3VO4. Mg++ inhibits the enzyme half-maximally at 3 mM, Ca++ stimulates at low and inhibits at high concentrations (half-maximally at 0.8 mM). The enzyme is supposed to be located at the inner side of the cell membrane. Vanadate has been proposed as an ideal regulator of active cation transport across the cell membrane. The finding of a HADH-vanadate-oxidoreductase converting vanadate into the rather inactive vanadyl further supports this hypotheses. The amount of vanadate at active sites of the target enzymes might be responsible for the known vanadate effects.
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PMID:Significance of NADH-vanadate-oxidoreductase of cardiac and erythrocyte cell membranes. 625 34

The influence of vanadium in the nominally +5 (NH4VO3; referred to as V5+), +4 (C10H14O5V and VOSO4; V4+) and +3 oxidation states (VCl3; V3+) on cardiac force of contraction, adenylate cyclase and (Na+ + K+)-ATPase activity was investigated in order to determine which form of vanadium mediates the cardiac effects. V5+, V4+ and V3+ (300 microM each) increased the force of contraction of isolated electrically driven cat papillary muscles by about 100%. In the presence of the reducing agent ascorbic acid (5 mM) none of the three compounds led to any distinct increase in force of contraction. On the particulate adenylate cyclase preparation from feline right ventricles only V5+ stimulated the enzyme activity by about 100%, whereas V4+ and V3+ were ineffective. In the presence of 5 mM ascorbic acid all three compounds were ineffective. In contrast, in the presence of the oxidizing agent diamide (azodicarboxylic acid-bis-dimethylamide; 1 mM) all three compounds became stimulatory. On the isolated (Na+ + K+)-ATPase V5+ (500 microM) alone reduced the basal activity by about 95%. In the presence of ascorbic acid the inhibitory effect of V5+ was greatly diminished. Similar results were obtained with V4+, V3+ (100 microM) alone inhibited (Na+ + K+)-ATPase activity only by about 40%. In the presence of ascorbic acid V3+ was ineffective. From the results it is concluded that positive inotropism, stimulation of adenylate cyclase and inhibition of (Na+ + K+)-ATPase by vanadium compounds likewise result from an action of vanadium in the +5 oxidation state.
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PMID:Effect of vanadium in the +5, +4 and +3 oxidation states on cardiac force of contraction, adenylate cyclase and (Na+ + K+)-ATPase activity. 629 2

Ionized forms of vanadium are known to exert diverse biological activities. Of particular interest in the inhibitory action of the vanadium ion on (Na+ + K+)-ATPase. This report describes another action of the vanadium ion on the rabbit colonic epithelium. Micromolar quantities of vanadate, applied to the serosal side of the isolated rabbit colonic epithelium, result in a stimulation of electrogenic chloride secretion by this epithelium. Sodium transport is unaffected by the vanadium ion in the concentrations used in this study. It is proposed that the vanadyl ion activates adenylate cyclase and thereby initiates subsequent secretory events.
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PMID:Vanadium ion stimulation of chloride secretion by rabbit colonic epithelium. 630 80

Experiments have been carried out to characterize the influence of the positive inotropic trace element vanadium (used as Na3VO4) on beta-adrenergic receptor coupled adenylate cyclase activity from human myocardium. Na3VO4 (10(4)M) stimulates basal activity as well as isoprenaline (10 microM)- and Mg2+ (20 mM) activated enzyme activity 1.5-2.4-fold. In contrast, adenylate cyclase activity in the presence of maximally activating concentrations of Gpp(NH)p (10 microM) cannot be further increased by Na3VO4. The results confirm the assumption (5) that vanadate stimulates adenylate cyclase by interacting with the nucleotide-binding site of this enzyme.
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PMID:Stimulation of human cardiac adenylate cyclase by vanadate. 690 65