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)

An experimental model of myocardiopathy was induced in rhesus monkeys following noradrenaline (NA) infusion (20 ug/kg body wt/minute), for a period of 2 hours daily for three consecutive days. The animals were sacrificed after two hours (acute phase), forty-eight hours (sub-acute phase) and twenty-one days (chronic phase). Focal depletion of succinic dehydrogenase, increase in adenosine triphosphatase, acid phosphatase and appearance of large fat droplets in myocardial muscle was noted in the acute phase. Histopathological examination revealed focal edema, opacity and fuchsinorrhagia of the muscle fibres distributed in both the ventricles. Myofibrillar degeneration, myocytolysis and vacuolization with aggregation of lymphomononuclear cells were the significant features in the acute phase. During sub-acute and chronic phases, these features became less prominent and reparative changes with proliferation of fibroblasts became more marked. By the twenty-first day, irregular, focal scars replaced the necrosed myocardium. Ultrastructurally, heart muscle showed myofibrillar disorganisation, distortion of Z and A bands, dilatation of sarcoplasmic reticulum and swelling and rupture of mitochondria. Altered membrane permeability was evidenced by the presence of reaction products of horseradish peroxidase within the cardiac cells. In the reparative phase, however, myocytolytic changes regressed and collagen deposition was the prominent feature. This experimental study has several histological features simulating human cases of myocardial infarction without coronary occlusion.
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PMID:Catecholamine-induced experimental cardiomyopathy--a histopathological, histochemical and ultrastructural study. 259 40

1. The importance of insulin in diabetic gastro-intestinal complications has been postulated. The present study was designed to investigate short-term effect of insulin on different smooth muscles isolated from non-diabetic animals. 2. The contractile responses of isolated guinea-pig ileum to acetylcholine and histamine and the serotonin-induced contractions of rat stomach fundus strips were inhibited by insulin in a non-competitive manner. The contractions of rat vas deferens elicited by noradrenaline and tyramine were also inhibited in the presence of insulin. 3. Insulin caused dose-dependent relaxation on the isolated rat duodenum. The relaxing response to insulin was not affected in the presence of atropine, phentolamine, propranolol, nicotinic acid, tetrodotoxin, tetraethylammonium, ouabain and nifedipine. The relaxing effect of insulin on the isolated rat duodenum was inhibited by sodium orthovanadate, trifluoperazine, verapamil, aspirin and dexamethasone, non-competitively. 4. The above results strongly suggest that the relaxing or inhibitory effect of insulin on the smooth muscles is closely related with prostanoid metabolism. Furthermore, it is concluded that this effect of insulin on the smooth muscles may be due to activation of Ca2+-pump ATPase(s).
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PMID:Insulin action on different smooth muscle preparations. 266 56

Experiments to determine the effects of the catecholamine neuronal uptake blockers cocaine and desipramine, and of the cardiac glycoside, ouabain, upon 3H-(noradrenaline) efflux have been performed with bovine adrenal medullary chromaffin cells in tissue culture. Both cocaine and desipramine reduced 3H-noradrenaline uptake into chromaffin cells. Inhibitable uptake was 80% of total accumulation over 60 min; this degree of inhibition was produced by cocaine (30 mumol/l) or desipramine (1 mumol/l). Cocaine (30 mumol/l) had no effect upon spontaneous 3H-efflux measured over 60 min, but reduced that evoked over the same period by carbachol (EC50), veratridine (EC50) and by ouabain (100 mumol/l). Cocaine did not reduce that efflux evoked by raised levels of K+ (28 mmol/l; EC50). Desipramine (1 mumol/l), like cocaine, had no effect upon spontaneous efflux of 3H, but reduced that efflux evoked by carbachol, veratridine and ouabain. Tetrodotoxin (TTX) inhibited veratridine-evoked 3H efflux (IC50 0.2 mumol/l). The degree of inhibition caused by TTX (0.2 mumol/l) was not increased by cocaine (30 mumol/l). TTX also inhibited ouabain-evoked 3H efflux: this was reduced by 55% by a concentration of TTX (1 mumol/l) sufficient to virtually abolish veratridine-evoked efflux. Cocaine (30 mumol/l) in the presence of TTX (1 mumol/l) did not further inhibit ouabain-evoked efflux. Cocaine (30 mumol/l) did not alter 86Rb+ uptake into chromaffin cells, nor did it alter that inhibition of 86Rb+ uptake produced by ouabain (100 mumol/l) indicating that cocaine has no effect upon Na,K-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Multiple effects of cocaine upon evoked secretion in bovine adrenal medullary chromaffin cells. Additional insight into the mechanism of action of cardiac glycosides. 272 5

The purpose of the present study is to determine the role of Na+,K+-ATPase in adrenergic neurotransmission of hypertension. Isolated perfused mesenteric vasculatures were prepared from spontaneously hypertensive rats (SHR, Okamoto and Aoki, 7-10 weeks old) and age-matched normotensive Wistar Kyoto rats (WKY). The effects of ouabain, a Na+,K+-ATPase inhibitor, on the norepinephrine overflow from the sympathetic nerve endings were examined. Norepinephrine overflow from the nerve endings as well as pressor responses during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the norepinephrine overflow evoked by electrical nerve stimulation, even in the presence of an uptake-blocker of norepinephrine. Further, the facilitatory effect of ouabain on stimulation-induced norepinephrine overflow was more prominent in SHR than in WKY. These results suggested that ouabain-sensitive Na+,K+-ATPase on sympathetic nerve terminals could have an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR compared with WKY.
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PMID:Effects of ouabain on adrenergic neurotransmission in spontaneously hypertensive rats. 283 72

The K+-induced hyperpolarization of Na-loaded mouse diaphragm muscle, enzymatic activity of Na,K-ATPase and 3H-ouabain binding to rat brain microsomes was measured in the presence of K+ channel blockers tetraethylammonium (TEA), tetrabutylammonium (TBA) and apamin. TBA, and to a lesser extent TEA in millimolar concentrations, inhibited the electrogenic effect of the Na,K pump, Na,K-ATPase activity, and 3H-ouabain binding. The inhibition of 3H-ouabain binding by TEA or TBA was more evident in the presence of ATP and Na+ ions. Apamin in nanomolar concentrations inhibited the electrogenic effect of Na,K pump and Na,K-ATPase but not the 3H-ouabain binding. The hyperpolarizing effects of insulin and NADH, but not that of noradrenaline, were also prevented by apamin. The inhibition of Na,K pump by TEA and TBA is apparently due to both competition with K+ for a binding site on the Na,K-ATPase and a reduction in the number of transporting sites. The site of action of apamin on Na,K-ATPase is different from that of tetra-alkylammonium compounds; it apparently decreases the turnover rate of the enzyme.
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PMID:Inhibition of the electrogenic Na,K pump and Na,K-ATPase activity by tetraethylammonium, tetrabutylammonium, and apamin. 283 45

Noradrenaline potently antagonizes the effects of N-methyl-D-aspartate (NMDA) (80 microM) on cyclic GMP production in immature rat cerebellar slices in vitro (IC50 = 0.6 microM). The effect is stereospecific (D-noradrenaline, IC50 = 100 microM), and also observed with adrenaline (IC50 = 0.5 microM) and isoprenaline (IC50 = 1.2 microM). The alpha 1-adrenoceptor agonists methoxamine or phenylephrine or the mixed alpha 1/alpha 2 agonists oxymetazoline or xylometazoline (100 microM) do not block the effects of NMDA, but the alpha 2-adrenoceptor agonist clonidine is weakly active (IC50 = 200 microM). Salbutamol and terbutaline were also inactive except at high concentrations (300 microM), as were a number of other catechol and phenylethylamine derivatives. The antagonistic effects of noradrenaline on the NMDA response were insensitive to phentolamine, atenolol, or propranolol (up to 100 microM), but were blocked by the alpha 2 antagonist idazoxan (1-10 microM). The Na+,K+-ATPase inhibitor ouabain (0.1-10 microM) markedly potentiates the effects of NMDA in this model, and also antagonizes and reverses the ability of noradrenaline (10 microM) to block the effects of NMDA. The results suggest that noradrenaline and Na+,K+-ATPase activity have potent modulatory effects on the NMDA response.
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PMID:Noradrenaline antagonizes and ouabain potentiates the effects of N-methyl-D-aspartate on rat cerebellar cyclic GMP production. 284 58

We investigated the effects of adrenalectomy or dexamethasone treatment on the regulation of brain (Na+,K+)-ATPase by noradrenaline. Noradrenergic stimulation was produced by repeated injections of yohimbine, and noradrenaline depletion by an injection of the selective toxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine). Adrenalectomy had no effect on the number of ouabain binding sites in cerebral cortex, but increased the number of sites synergistically with noradrenergic stimulation. Dexamethasone prevented the decrease in ouabain binding in rats treated with DSP4, but did not itself alter ouabain binding. Neither dexamethasone nor adrenalectomy altered the changes in beta-receptor binding associated with the noradrenergic manipulations. Changes in exposure to corticosteroids may alter the coupling between adrenoceptor binding and second messenger activation in a way that affects (Na+,K+)-ATPase regulation.
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PMID:Dexamethasone and adrenalectomy alter brain (Na+,K+)-ATPase responses to noradrenergic stimulation or depletion. 285 59

In order to evaluate endogenous Na+,K+-ATPase inhibitor on sympathetic nerve endings, endogenous Na+,K+-ATPase inhibitor and plasma noradrenaline were determined in patients with essential hypertension under different sodium conditions. Compared with the plasma from non-salt-sensitive patients, that from salt-sensitive patients showed significantly higher Na+,K+-ATPase inhibitor and plasma noradrenaline levels. Salt-induced changes in endogenous Na+,K+-ATPase inhibitor and those in blood pressure or plasma noradrenaline showed positive correlations. These results suggest that the salt-induced increase in endogenous Na+,K+-ATPase inhibitor might induce blood pressure elevation in essential hypertension, at least partly via increased noradrenaline levels.
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PMID:Relationship between the sympathetic nervous system and sodium potassium adenosine triphosphatase inhibitor in salt-sensitive patients with essential hypertension. 285 28

The relationship between changes in the pressor response to infused noradrenaline induced by intravenous injection of ouabain, an Na+,K+-ATPase inhibitor, and plasma renin activity and plasma ionized calcium was examined in 16 normotensive subjects and in 16 patients with essential hypertension. These patients were divided into 11 normal-renin and five low-renin essential hypertensives. The pressor response was significantly greater in low-renin hypertensives than in normotensives and normal-renin hypertensives. Following the injection of ouabain, the pressor response was significantly increased with no change in basal levels of blood pressure, plasma noradrenaline concentration, plasma calcium and plasma parathyroid hormone in both normotensives and essential hypertensives. The pressor response to noradrenaline was negatively correlated with levels of plasma noradrenaline and calcium after the injection of ouabain as well as before the injection in normotensives and essential hypertensives. The regression line between the pressor response and that of plasma noradrenaline or plasma calcium was significantly shifted towards a higher pressor response in normotensives, but not in essential hypertensives. The changes in the pressor response to noradrenaline induced by the injection of ouabain was significantly smaller in essential hypertensives, particularly in low-renin hypertensives, compared with normotensives. These results suggest that: (1) ouabain increases the pressor response to noradrenaline; (2) this increase is related to calcium metabolism; (3) endogenous Na+,K+-ATPase inhibitor(s) might be elevated in essential hypertensives; and (4) an increase in endogenous Na+,K+-ATPase inhibitor might, therefore contribute to an enhanced noradrenaline response in essential hypertensives, particularly in low-renin hypertensives.
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PMID:The effect of ouabain on pressor responses to infused noradrenaline in patients with essential hypertension. 285 44

Norepinephrine (NE) sensitization of rat brain Na+ -K+ ATPase to ethanol (EtOH) inhibition appears to be mediated by alpha 1-adrenoreceptors, since it was reversed by prazosin and WB-4101 (alpha 1-receptor antagonists) in a concentration-dependent manner, but not by yohimbine and piperoxan (alpha 2-receptor antagonists). In addition, clonidine (alpha 2-agonist) and methoxamine (central receptor type uncertain) produced very little sensitization. Chronic EtOH administration to rats for 3 weeks produced tolerance to the hypothermic effect of test doses of EtOH (3 g/kg, i.p.) and a decreased inhibitory effect of NE + EtOH on the enzyme in vitro. This inhibition was still prevented by prazosin and WB-4101. However, the binding of tritiated WB-4101 and prazosin to brain membrane preparations from control and EtOH-tolerant rats revealed that the maximum number of binding sites (Bmax) and the dissociation constant (KD) of alpha 1-adrenoreceptors were decreased after tolerance development. These changes in numbers and binding properties of alpha 1-adrenoreceptors probably account for the decreased NE sensitization of the ATPase to EtOH inhibition in preparations from EtOH-tolerant rats.
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PMID:Alpha 1-adrenergic receptor involvement in norepinephrine-ethanol inhibition of rat brain Na+ -K+ ATPase and in ethanol tolerance. 286 93


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