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)

We investigated the hypothesis that ouabain would reduce energy expenditure in the hypothermic, ischemic heart by inhibiting membrane-bound sodium/potassium-activated adenosine triphosphatase and lead to improved function on reperfusion. Additionally, we compared ouabain with another potential adjunct, the calcium channel blocker verapamil. The isolated rabbit heart was used as a model, and three experimental groups were studied after 1, 6, 12, and 24 hours of 4 degrees C ischemia. Hearts in group I were stored in a standard high potassium solution; hearts in groups II and III were stored in the same solution supplemented with verapamil (2 mg/L) and ouabain (3 mg/L), respectively. After ischemia, all hearts were reperfused for 45 minutes on a modified Langendorff apparatus, and left ventricular function was measured before freeze-clamping the heart for metabolite determination. At 1 and 6 hours, hearts in all groups functioned well, but the group III hearts had higher levels of adenosine triphosphate, phosphocreatine, total adenine nucleotides, and glycogen. After 12 hours of ischemia, function was significantly better in group III hearts (p less than 0.01) compared with that of hearts in groups I and II. Group III hearts also exhibited higher levels of high energy phosphates and glycogen. After 24 hours of storage, all hearts functioned poorly, and there was a marked decline in measured metabolites. Although we could show no improvement with the addition of verapamil, ventricular function was improved after storage in a high potassium hypothermic solution containing ouabain. Because ouabain inhibits the hydrolysis of adenosine triphosphate by sodium/potassium-activated adenosine triphosphatase, this result suggests that the glycoside maintains energy-rich phosphates necessary for optimal resumption of cardiac function.
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PMID:Improved recovery of cardiac function after hypothermic ischemic storage with ouabain. 284 69

The Ca2+-adenosine triphosphatase (ATPase) of skeletal muscle sarcoplasmic reticulum is a single protein species that pumps calcium ions at the expense of adenosine triphosphate (ATP). The reaction cycle includes phosphorylated intermediates which change the affinity and orientation of calcium sites. The monomer appears to be fully functional. Cross-linking and fluorescence studies indicate that ATP binds to a domain that approaches the phosphorylation site and becomes occluded during the reaction cycle. Interactions between these and the calcium channel, possibly via an energy transduction domain, ensure efficient coupling of catalytic and transport cycles.
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PMID:Mechanism of action of the calcium pump of sarcoplasmic reticulum of skeletal muscle. 296 Oct 95

The human red blood cell was used as a model system in order to study the effect of cholesterol and its medically important oxidized derivatives (OSC = oxidized sterol compounds) on the calcium entry channel. The calcium-ejecting adenosine triphosphatase (ATPase) was inhibited by vanadate and the influx of 45Ca2-into the cells measured. The cells were loaded with OSC at concentrations between 0.075 and 1.5 micrograms OSC/10(7) cells. Two classes of OSC could be distinguished: one stimulating Ca2+ influx dose-dependently by almost 100% at maximum concentrations, the other inhibiting it dose-dependently by up to 80%. The calcium channel blocker nitrendipine inhibited influx by 70% at 15 microM. More than 90% of the total stimulation or inhibition was accounted for by an influence on the nitrendipine-inhibitable part of influx, i.e. the calcium channel. Cholesterol (incorporated using liposomes) had a stimulatory (+288%), cholesterol depletion an inhibitory effect on calcium influx (-18%). These results demonstrate that cholesterol and its oxidized derivatives modulate the calcium channel in a highly stereospecific manner and provide new insights into the mechanism of action and the atherogenic effect of these compounds.
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PMID:Cholesterol and its oxidized derivatives modulate the calcium channel in human red blood cells. 610 Jul 51

It has recently been shown that two novel tachykinins, ranakinin and [Leu3, Ile7]neurokinin A, are present in fibers innervating the frog adrenal gland, and it has been demonstrated that tachykinins stimulate corticosteroid secretion in vitro through activation of chromaffin cells. The purpose of the present study was to investigate the effect of ranakinin on cytosolic free calcium concentrations ([Ca2+]i) and to determine the source of calcium involved. Cultured adrenal cells were loaded with the fluorescent calcium indicator indo-1, and changes in [Ca2+]i were studied using dual emission wavelength microfluorimetry. Administration of a brief pulse of ranakinin (1 microM; 1 sec) in the vicinity of chromaffin cells caused an immediate and transient increase in [Ca2+]i. Repeated pulses of ranakinin resulted in a gradual decline in the [Ca2+]i response, suggesting the occurrence of a desensitization phenomenon. Preincubation of the cells with the calcium channel blockers nifedipine (10 microM) and omega-conotoxin (1 microM) did not alter the response of chromaffin cells to ranakinin. Chelation of extracellular calcium by EGTA (10 mM) caused a marked decrease in the basal [Ca2+]i, but did not suppress the ranakinin-induced [Ca2+]i increase. Conversely, incubation of the cells with thapsigargin (10 microM), an inhibitor of calcium adenosine triphosphatase activity, abolished the stimulatory effect of ranakinin, indicating that the increase in [Ca2+]i can be ascribed to mobilization of calcium from intracellular stores. Preincubation of adrenal cells with the phospholipase C antagonist U-73122 (1 microM; 18 min) or with pertussis toxin (10 microM; 18 h) totally blocked the ranakinin-induced [Ca2+]i rise. Taken together, these data indicate that in frog adrenochromaffin cells, ranakinin causes mobilization of calcium from intracellular stores. The effect of ranakinin is mediated through activation of a phospholipase C via a pertussis toxin-sensitive G protein.
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PMID:Effect of ranakinin, a novel tachykinin, on cytosolic free calcium in frog adrenochromaffin cells. 766 74

The inositol 1,4,5-trisphosphate receptor (IP3R) is an endoplasmic reticular calcium release channel found in most cell types. Calcium signaling mediated by IP3Rs regulates a wide variety of physiological processes, including smooth muscle contraction, immune function, and fertility. We have focused on the role of the IP3R in programmed cell death and the regulation of IP3R levels in heart failure, a condition shown to be associated with cardiomyocyte apoptosis. During end-stage human heart failure, we have demonstrated that type 1 IP3R (IP3R1) mRNA and protein levels are up-regulated, in contrast to other cardiac calcium regulatory proteins, such as the type 2 ryanodine receptor (RYR2) and type IIa sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2), which are down-regulated. These data suggest that altered calcium channel expression may contribute to the defects in calcium homeostasis during heart failure. Furthermore, regulation of the IP3R may have implications for the survival of cardiac myocytes. Data from our laboratory have linked IP3R expression with susceptibility to apoptosis. IP3R-deficient T cells are resistant to apoptosis induced by dexamethasone, T cell receptor stimulation, ionizing radiation, and Fas. These findings suggest that intracellular calcium release via IP3Rs is a critical mediator of apoptosis. Thus the IP3R, which is up-regulated during human heart failure, may play a role in cardiomyocyte apoptosis and therefore in the pathophysiology of heart failure.
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PMID:Role of inositol 1,4,5-trisphosphate receptors in regulating apoptotic signaling and heart failure. 947 44

It is unknown whether there are regional differences in the change of atrial effective refractory period (ERP) after a short duration of rapid atrial pacing. Furthermore, the effects of calcium channel and potassium channel on this phenomenon have not been extensively investigated. In opened-chest dogs, the endocardial monophasic action potential duration at 90% repolarization (APD90) from the right atrial appendage, and ERP from seven atrial sites were measured before and after rapid atrial pacing at 800 beats/min for 30 minutes. Both atrial ERP and APD90 significantly shortened after rapid atrial pacing. The postpacing atrial ERP and APD90 shortening persisted for 119 +/- 3 and 123 +/- 4 seconds after cessation of pacing, respectively. There was no significant difference in the magnitude or recovery course of atrial ERP shortening after pacing among the seven atrial sites. Pretreatment with nicorandil and d-sotalol had no effects on the magnitude or recovery course of atrial ERP shortening after pacing. However, the degree of ERP and APD90 shortening after pacing was significantly attenuated in the verapamil and ryanodine groups; furthermore, the recovery of ERP and APD90 after cessation of pacing was faster in the two groups. In conclusion, shortening of atrial ERP induced by short-duration rapid atrial pacing was uniform in both atria. Both the adenosine triphosphatase (ATP) dependent potassium current and rapid component of the delayed rectifier did not significantly influence this phenomenon, but both the verapamil and ryanodine could significantly attenuate the degree of atrial ERP and APD90 shortening.
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PMID:Change of atrial refractory period after short duration of rapid atrial pacing: regional differences and possible mechanisms. 1039 91

19-Nor-1,25-dihydroxyvitamin D(2) (19-norD(2)) a less calcemic and phosphatemic analog of 1,25-dihydroxyvitamin D (1,25[OH](2)D(3)), is approved for the treatment of secondary hyperparathyroidism in patients with kidney failure. We have previously demonstrated that 19-norD(2) is less active than 1,25(OH)(2)D(3) in stimulating bone resorption. In this study, we compared the potencies of 19-norD(2) and 1,25(OH)(2)D(3) in stimulating net calcium and phosphate absorption in the intestine. Mineral balance was assessed in normal rats during the last 4 days of a 14-day treatment with various daily doses of 19-norD(2) or 1,25(OH)(2)D(3). Calcium absorption increased from 16.5% +/- 7.8% in vehicle-treated rats to 27.5% +/- 7.2% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 21.6% +/- 3.9%, 26.2% +/- 5.5%, and 27.4% +/- 5.1% in rats treated with 10, 50, and 100 ng/day 19-norD(2), respectively. Thus comparable stimulation of calcium transport was attained with 10 ng 1,25(OH)(2)D(3) and 100 ng 19-norD(2). Similar results were obtained for phosphate absorption, with an increase from 28.2% +/- 5.5% in vehicle-treated rats to 40.2% +/- 4.7% in rats given 10 ng/day 1,25(OH)(2)D(3) and to 32.9% +/- 2.2%, 36.2% +/- 4.5%, and 36.8% +/- 3.8% in rats given 10, 50, and 100 ng/day 19-norD(2), respectively. Vitamin D compounds are believed to increase calcium absorption by inducing a calcium channel (epithelial calcium transporter or calcium transporter-1 [CaT1]) on the luminal membrane, a calcium-binding protein (Calbindin D9k) in the cytosol, and a calcium pump (plasma membrane calcium adenosine triphosphatase-1 [PMCA1]) on the basolateral membrane. Northern-blot analysis of intestinal ribonucleic acid of vitamin D-deficient rats given seven daily injections of vehicle or 100 ng 1,25(OH)(2)D(3) or 19-norD(2) revealed that 19-norD(2) was less potent than 1,25(OH)(2)D(3) in stimulating expression of CaT1, Calbindin D9k and PMCA1. In summary, the reduced calcemic and phosphatemic activities of 19-norD(2) can be attributed to lower potency in stimulating intestinal calcium and phosphate absorption.
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PMID:Differential effects of 19-nor-1,25-dihydroxyvitamin D(2) and 1,25-dihydroxyvitamin D(3) on intestinal calcium and phosphate transport. 1203 88

Changes in thyroid status markedly influence cardiac contractile and electrical activity. The predominant route by which triiodothyronine (T3) affects cardiac action is by exerting a direct effect in cardiac myocytes through binding to thyroid hormone nuclear receptor isoforms. In addition, T3 modifies cardiac action by alterations in the vascular system and decreases afterload of the left ventricle by subtle modification related to the sympathetic system. The importance of T3 nuclear receptor function has been further demonstrated by studies in null mutant mice in which thyroid hormone receptor-alpha (TRalpha) and thyroid hormone receptor-beta (TRbeta) or both are deleted. In mice with null mutations of the TRalpha, a markedly decreased heart rate and decreased contractile performance occurs in contrast to mice with deletion of TRbeta that have a normal heart rate and a normal contractile performance under baseline conditions. Thyroid hormone influences on heart rate are exerted by specific ion channel proteins in the sinus node of the left atrium. Some of these ion channels, such as the IF channel, the sodium/calcium exchanger protein, the L-type and T-type calcium channel, and the ryanodine channel are targets for thyroid hormone action. The increased contractile performance induced by T3 is largely mediated by increased expression of the calcium adenosine triphosphatase (ATPase) of the sarcoplasmic reticulum and decreased expression of phospholamban and T3 increases the phosphorylation status of phospholamban. The significant influence that is exerted by thyroid hormone signaling system related to contractile and electrical activity in the heart and the molecular basis for these alterations continues to be clarified.
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PMID:Cellular action of thyroid hormone on the heart. 1216 5

This article will review the cardiovascular toxicities of various medications, stressing the electrocardiographic presentation--both rhythm and morphological issues--and emphasizing recognition and management issues. Cardiovascular toxins are grouped into categories causing similar electrocardiographic effects, including the potassium efflux blockers, sodium channel blockers, sodium-potassium adenosine triphosphatase blockers (ie, digitalis compounds), calcium channel blockers, and beta-adrenergic blockers. This article reviews the various electrocardiographic abnormalities associated with these 5 classes of agents, ranging from morphological abnormalities and conduction blocks to brady- and tachyarrhythmias.
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PMID:Electrocardiographic abnormalities associated with poisoning. 1760 94