Gene/Protein Disease Symptom Drug Enzyme Compound
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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 cardioprotective agents prenylamine and glyceryl trinitrate (GTN) with respect to their effects on the bioenergetics of catecholamine storage vesicles. Chromaffin granule ghosts, which have a well preserved ability to actively transport and store catecholamines, were used as a model for adrenergic synaptic vesicles due to their functional similarity. Prenylamine, which partially and reversibly deplete the endogenous stores of noradrenaline in adrenergic nerves and ganglia, was found to inhibit the generation of the transmembrane proton electrochemical gradient driven by a H(+)-ATPase, mainly by acting as an uncoupler of this ATPase. The inhibition of the energy dependent dopamine uptake (and noradrenaline biosynthesis) by prenylamine could be accounted for by its effect on the bioenergetics of the storage vesicles. The organic nitrates glyceryl trinitrate and isosorbide dinitrate also partly inhibited the catecholamine uptake in parallel with their effects on the proton electrochemical gradient. It is concluded that GTN is a weak catecholamine depletor. Experiments with 3-morpholinosydnonimin-hydrochloride, a source of nitric oxide (NO), opens up the possibility that the mechanism of inhibition of the bioenergetics of chromaffin granule ghosts by GTN is mediated by NO.
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PMID:The effect of prenylamine and organic nitrates on the bioenergetics of bovine catecholamine storage vesicles. 214 83

To clarify the role of Na,K-ATPase inhibitor in the enhanced pressor response to infused noradrenaline (NA-R) in patients with benign essential hypertension (EHT), NA-R, plasma noradrenaline concentration (PNA), and blood ionized calcium (Ca2+) were investigated before and after intravenous injection of ouabain in 15 normotensive subjects (NT) and 13 EHT. NA-R was enhanced by ouabain in both NT and EHT. The augmentation of NA-R following ouabain injection (delta NA-R) and % delta NA-R were significantly lower in EHT than in NT. Following ouabain injection, no significant change in PNA and blood Ca2+ was observed in both NT and EHT. NA-R negatively correlated with PNA and blood Ca2+, which were estimated just prior to noradrenaline infusion, before ouabain injection as well as after. After ouabain, the regression line between NA-R and PNA or blood Ca2+ shifted toward higher NA-R level in NT, unlike in EHT. These results suggest that an exogenous Na,K-ATPase inhibitor brings about a blunted enhancement of NA-R in EHT consistent with the presence of an endogenous Na,K-ATPase inhibitor in EHT.
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PMID:The role of Na,K-ATPase inhibitor on pressor responsiveness in patients with benign essential hypertension. 215 65

Effects of morphine on noradrenaline release from rat cerebrocortical synaptosomes and on the Na+,K(+)-ATPase activity in homogenates of synaptosomes and of synaptic membranes were examined. Both morphine (10(-3)-10(-5) M) and methionine-enkephalin (M-Enk; 10(-5) M) inhibited the enhanced [3H]noradrenaline [( 3H]NA) release evoked by high concentrations of K+ from synaptosomes and these inhibitory actions were antagonized by naloxone (10(-4), 10(-5) M). Morphine (10(-3)-10(-5) M) and M-Enk (10(-5) M) stimulated the Na+,K(+)-ATPase activity in homogenates of synaptosomes but not of synaptic membranes in the incubation medium containing 2.2 X 10(-6)-4.7 X 10(-7) M free Ca2+ and these stimulatory effects were antagonized by naloxone. In homogenates of synaptic membranes, the same concentrations of morphine and M-Enk stimulated the Na+,K(+)-ATPase activity suppressed by FeCl2 (5 X 10(-7) M) but not by CuCl2 nor ZnCl2, and these stimulatory effects were antagonized by naloxone. Significant levels of Fe2+ were liberated from synaptosomes during the preparation of synaptic membrane using distilled water. These results suggest that both morphine and M-Enk stimulate the suppressed Na+,K(+)-ATPase activity by interacting with Fe2+ at opioid receptor sites, and they may play a role in the suppression of membrane depolarization and/or the release of NA through their stimulatory action on the Na+,K(+)-ATPase activity probably suppressed by Fe2+ in the rat cerebral cortex.
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PMID:Effect of morphine on Na+,K(+)-ATPase from homogenate of synaptosomes and of synaptic membrane of rat cerebral cortex. 215 27

1. In the isolated perfused, noradrenaline (NA)-constricted mesenteric arteries of the rat, acetylcholine (0.003-1 nmol), histamine (0.01-10 nmol) and the calcium ionophore A23187 (0.01-1 nmol), caused endothelium-dependent vasodilatation while the vasodilatation by the K+ channel activator BRL 34915 (0.1-1 nmol) was independent of endothelium. 2. The guanylate cyclase inhibitor, methylene blue at 10 microM did not inhibit the action of any of the vasodilators but at 50 microM reduced the vasodilator effect of acetylcholine (ACh), histamine and A23187. 3. Infusion of ouabain or perfusion with K(+)-free or excess K+ (50 mM) Krebs solution reduced the vasodilator effect of ACh, histamine and A23187, suggesting the action of these agents involves, at least in part, activation of Na+/K(+)-ATPase. The vasodilator effect of BRL 34915 was not affected by ouabain, but abolished during perfusion with Krebs solution containing excess K+ or depleted of K+. 4. Five structurally distinct K+ channel blockers (apamin, crude scorpion venom, procaine, quinidine and tetraethylammonium) attenuated the vasodilator effect of ACh, histamine and A23187. The K+ channel blockers, except apamin and crude scorpion venom, also inhibited the vasodilatation produced by BRL 34915. 5. The vasodilator effect of ACh, histamine or A23187 was not altered in mesenteric vessels of pertussis toxin-treated rats, suggesting that the K+ channels associated with the endothelium-dependent vasodilator effect of these agents are either not coupled to G-proteins or are coupled to G-proteins that are insensitive to pertussis toxin. 6. The calcium channel blockers, diltiazem (0.1 or 1 microM), nifedipine (0.01 or 0.1 microM) or nitrendipine (1 nM) attenuated the vasodilatation produced by ACh, histamine, A23187 and also that by BRL 34915. 7. We conclude that endothelium-dependent vasodilatation induced by ACh, histamine and A23187 is mediated via activation of membrane K+ channels and Na+/K+-ATPase. The K+ channels involved in the vasodilator action of these agents are not coupled to pertussis toxin-sensitive G-proteins and appear to be regulated by Ca2 +.
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PMID:Endothelium-dependent and BRL 34915-induced vasodilatation in rat isolated perfused mesenteric arteries: role of G-proteins, K+ and calcium channels. 216 32

Using hepatocytes isolated by collagenase perfusion, we studied the accumulation of 3H-noradrenaline. Cells incubated during 15 min in the presence of 0.4 mumol/l 3H-noradrenaline (without inhibition of noradrenaline metabolism) accumulated 8.32 +/- 1.77 pmol/10(6) cells (n = 3). The accumulation of 3H-noradrenaline in isolated parenchymal liver cells was sensitive to 10 mumol/l cocaine (inhibition 36.6 +/- 7.9%, n = 3) and 1 mumol/l desipramine (inhibition 27.2 +/- 6.9, n = 3). Accumulation of 3H-noradrenaline was temperature and sodium dependent (inhibition 33.2 +/- 9.4%, n = 9, when Na+ was replaced by Tris+) and was influenced by the inhibition of the membrane Na(+)-K(+)-adenosine triphosphatase (Na(+)-K(+)-ATPase) by 150 mumol/l ouabain (34.7 +/- 6.9% inhibition, n = 3). Accumulation of 3H-noradrenaline in the hepatocytes was not affected by the presence of uptake2 inhibitors, normetanephrine (30 mumol/l) and corticosterone (30 mumol/l), but was reduced by 30 mumol/l isoprenaline (76.3 +/- 5.0% inhibition, n = 6). Thus, the system that takes up and accumulates noradrenaline in the isolated rat liver cells possesses some characteristics of both, uptake1 and uptake2 systems and appears to be different from other extraneuronal cocaine-sensitive systems, such as the one reported for pulmonary endothelial cells.
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PMID:Accumulation of 3H-(+/-)-noradrenaline by isolated rat liver cells. 216 96

The effects of calcium and deoxycorticosterone (DOC) were studied in four groups of spontaneously hypertensive rats (SHR): control, calcium, DOC and DOC + calcium. Calcium was administered in drinking fluid as 1.5% calcium chloride, and DOC was injected weekly (25 mg/kg subcutaneously). During the 9-week study the increase in systolic blood pressure was enhanced in the DOC and attenuated in the calcium group, but did not differ from control values in the DOC + calcium group. DOC augmented in vitro contractions of aortic and mesenteric arterial rings induced by noradrenaline and impaired relaxations in response to nitroprusside and acetylcholine. Calcium alone enhanced the relaxation in response to nitroprusside in the mesenteric artery. In the DOC + calcium group vascular contractions did not differ from control values, but the relaxations caused by nitroprusside and acetylcholine were augmented in the mesenteric artery. The activity of erythrocyte Ca2(+)-ATPase increased in both calcium groups. The Na+:K+ ratio of tail artery tissue was reduced in the calcium group. In conclusion, calcium supplementation attenuates the development of hypertension, and prevents DOC-induced blood pressure increases in SHR by altering vascular reactivity. Changes in smooth muscle electrolyte ratios and Ca2(+)-ATPase activity may account for these alterations.
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PMID:Effects of a high calcium diet and deoxycorticosterone on vascular smooth muscle responses in spontaneously hypertensive rats. 217 73

1. The kidney taken from a rat rendered nephrotic by exposure to puromycin aminonucleoside retains sodium abnormally when perfused in isolation and has an abnormally low vascular resistance (J. D. Firth et al., Clin. Sci. 1989; 76, 387-95). In this study the relation of oxygen consumption to sodium reabsorption has been examined in the isolated nephrotic organ, which has also been exposed to a variety of natriuretic agents and to the effect of inhibition of metabolism by cooling, in an attempt to discern the transport process, or processes, responsible for abnormal tubular handling of sodium. In addition, the effects of three endogenous vasoconstrictors, noradrenaline, angiotensin II and endothelin, on the function of the isolated nephrotic kidney have been examined. 2. The ratio of mol of sodium reabsorbed by the tubules of the isolated nephrotic kidney to mol of oxygen consumed was reduced in comparison with the control kidney (means +/- SEM): 9.22 +/- 0.97 versus 15.43 +/- 1.55 (P less than 0.002). 3. In the presence of ouabain (1 mmol/l), acetazolamide (1 mmol/l), frusemide (200 mumol/l), the combination of these three agents together, hydroflumethiazide (100 mumol/l), benzamil (100 nmol/l) or atrial natriuretic peptide (1000 pmol/l), a lesser increment in sodium excretion was induced in the isolated nephrotic kidney than in the control kidney and the nephrotic organ continued to excrete less sodium in both absolute and fractional terms. 4. This suggests that enhanced tubular sodium reabsorption in the isolated nephrotic kidney does not depend upon abnormally increased activity of the Na+/K(+)-adenosine triphosphatase, bicarbonate-dependent sodium transport, Na+/K+/2Cl- co-transport, electrically neutral proportionate reabsorption of sodium and chloride (distal tubule), epithelial sodium channel (distal tubule) or atrial natriuretic peptide-sensitive sodium transport processes. 5. When isolated nephrotic kidneys and normal kidneys were cooled to 8-10 degrees C the handling of sodium became virtually identical in the two groups. On re-warming to 37 degrees C, the original differences in sodium handling between nephrotic and control kidneys were restored. This implies that the mechanism responsible for the abnormal tendency to retain sodium is temperature-sensitive; as yet it remains otherwise undefined. 6. The sensitivity of the renal vessels to noradrenaline, angiotension II and endothelin, as judged by the percentage reduction in perfusate flow rate produced by a given concentration of any of these agents, was not substantially altered in the nephrotic kidney compared with the control kidney. Increase in vascular tone was not associated with amelioration of the tendency of the isolated nephrotic organ to retain sodium. Increasing concentrations of angiotensin II caused the filtration rate to increase in the nephrotic kidney. This effect was unexpected: in the control preparation, as anticipated, angiotensin II caused the filtration rate to decrease.
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PMID:Effect of natriuretic agents, vasoactive agents and of the inhibition of metabolism on sodium handling in the isolated perfused kidney of the nephrotic rat. 217 43

1. Suramin, an inhibitor of several types of ATPase, was investigated for its ability to antagonize responses mediated via P2X-purinoceptors in the guinea-pig urinary bladder and P2Y-purinoceptors in the guinea-pig taenia coli. 2. In isolated strips of bladder detrusor muscle, suramin (100 microM-1 mM) caused a non-competitive antagonism of responses to alpha, beta-methylene ATP with an estimated pA2 of approximately 4.7, and inhibited responses to stimulation of the intramural purinergic nerves, with a similar pA2 value. At a concentration of 10 microM, suramin had little effect, but at a concentration of 1 microM, suramin potentiated responses to alpha,beta-methylene ATP, and potentiated responses to electrical stimulation of intramural purinergic nerves. 3. In isolated strips of taenia coli, in which a standard tone had been induced by carbachol (100 nM), suramin at 100 microM and 1 mM significantly antagonized relaxant responses to ATP (at an EC50 concentration) with an estimated pA2 of 5.0 +/- 0.82 and relaxant responses to electrical stimulation of the intramural non-adrenergic, non-cholinergic inhibitory nerves, either single pulses or trains of 8 Hz for 10 s, with estimated pA2 values of 4.9 +/- 0.93 and 4.6 +/- 1.01, respectively. Suramin had no significant effect at 1 or 10 microM. 4. Suramin, at any of the concentrations tested, did not affect contractile responses to histamine (10 microM) or carbachol (10 microM) in the bladder detrusor preparations. In the taenia coli, suramin did not affect either the relaxant responses to noradrenaline (at an EC50 concentration) or the contractile responses to carbachol (100 nM). 5. Thus, suramin at concentrations above 10 microM blocked actions mediated via P2x- and P2y-purinoceptors in the guinea-pig urinary bladder and taenia coli respectively. Potentiation of purinoceptor-mediated activity was seen only at a low concentration of suramin (1 microM) and only in the urinary bladder (P2x-purinoceptor). For its antagonistic activity suramin did not discriminate between P2X- and P2y-purinoceptors, but it was selective for P2-purinoceptor-mediated activity rather than that mediated via cholinoceptors, adrenoceptors or histamine receptors.
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PMID:Suramin antagonizes responses to P2-purinoceptor agonists and purinergic nerve stimulation in the guinea-pig urinary bladder and taenia coli. 233 85

Adrenaline markedly increased the ouabain-sensitive 22Na+-efflux by stimulating the Na+-K+ pump in frog skeletal muscle. The facilitatory effects of adrenaline had the following properties. The effects of adrenaline on the ouabain-sensitive Na+-efflux were observed at concentrations greater than 0.1 microM and the magnitude increased with concentration up to 10 microM. At a concentration of 30 microM, adrenaline markedly augmented the ouabain-sensitive Na+-efflux, but other biogenic amines were less effective (noradrenaline and dopamine) or ineffective (histamine and serotonin). The increase of Na+-efflux induced by 1 microM adrenaline was blocked by 3 microM propranolol, but not by 3 microM phenoxybenzamine. The properties of the facilitatory action of adrenaline on the ouabain-sensitive Na+-efflux suggest that beta-adrenoceptors have an important role in modulating the Na+-K+ pump activity in the skeletal muscle membrane. The protein complex localized in excitable membranes, namely the Na+-K+ ATPase-beta-adrenoceptor complex, may be the functional unit which operates the membrane machinery driving the Na+-K+ pump.
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PMID:Beta-adrenergic modulation of the Na+-K+ pump in frog skeletal muscles. 241 22

Triethyltin (TET) salt intoxication provokes a myelinic vacuolisation associated with a white matter cerebral edema. The central nervous system disturbances accompanying these phenomena (Na-K-ATPase activity, neurological symptoms, water and sodium cerebral content) can be counteracted by drugs used in age-related brain failure; consequently, TET intoxication could be suggested as an experimental model for studying the aging process. The aim of the present study is to follow-up the biogenic amine concentrations in different brain areas of TET treated rats, knowing that modifications of cerebral amines exist throughout the aging process. The following results are obtained: the cerebral water content of the TET treated rats is significantly increased, confirming the existence of a brain edema. Monoamine concentrations are significantly decreased, specifically noradrenaline (in hypothalamus, mesencephalon, cerebellum); serotonin (in striatum, hypothalamus, mesencephalon); dopamine only in hypothalamus; these are accompanied by an increase of the metabolites 5 HIAA (in striatum and mesencephalon) and HVA (striatum). These modifications are compared to those occurring in physiological aging, and hypothetical mechanisms are reviewed. We conclude that TET intoxication must not be considered as a pathophysiological model of brain aging, but may be considered as a useful pharmacological tool for studying experimental drugs liable to counteract brain age-induced disturbances.
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PMID:Effect of triethyltin chloride on the central aminergic neurotransmitters and their metabolites: relationship with pathophysiology of aging. 241 71


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