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)

Salmonella typhimurium, an organism that invades intestinal mucosa but does not elaborate a traditional enterotoxin, evokes ileal secretion by causing alterations in active sodium and chloride transport mechanisms. To evaluate the possibility that these changes in transport might be related to the adenylate cyclase-cyclic AMP or NA+-K+-adenosine triphosphatase (ATPase) systems, mucosal adenylate cyclase, cAMP phosphodiesterase, Na+-K+ and Mg++ ATPase activities, and cAMP concentrations were measured in rabbit ileal loops infected with two strains of S. typhimurium. Strain TML invades the mucosa and evokes fluid secretion whereas strain SL 1027 invades but does not evoke secretion. Cholera toxin-stimulated loops were also studied. When compared to control loops, TML-infected mucosa demonstrated a marked increase in adenylate cyclase activity, in cAMP concentration, and no change in phosphodiesterase or ATPase activities. SL 1027-infected mucosa demonstrated no change in either adenylate cyclase or ATPase activities. Indomethacin pretreatment of cyclase activation. In contrast, indomethacin pretreatment of cholera toxin exposed animals resulted in only a partial reduction of secretion while not altering the stimulation of adenylate cyclase. These results suggest that: (1) S. typhimurium causes ileal secretion by stimulating adenylate cyclase; (2) mucosal invasion alone (SL 1027) is not sufficient to activate adenylate cyclase, and (3) Na+-K+-ATPase does not appear to be involved in salmonella-induced secretion. The mechanism of salmonella activation of adenylate cyclase is unclear but apparently differs from that of cholera toxin in that it is inhibited by indomethacin. This might be explained by the participation of prostaglandins in the salmonella activation process.
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PMID:Pathogenesis of Salmonella-mediated intestinal fluid secretion. Activation of adenylate cyclase and inhibition by indomethacin. 17 99

The relationship between variations in diaphragmatic contractility and corresponding changes in total tissue levels of 45Ca and adenosine 3',5'-cyclic monophosphate (cAMP) was examined. The contractile performance of perfused contracting rat diaphragms was manipulated with theophylline (10(-4) M), induced fatigue, or both. The increased contractility associated with theophylline was related to significant increases in 45Ca levels without changes in cAMP levels. Fatigue-diminished contractility was associated with increases in both 45Ca and cAMP levels. The increased 45Ca and cAMP levels associated with fatigue persisted, even in the presence of theophylline. Calcium channel blockade with 10(-4) M verapamil blocked the positive inotropic influence of theophylline as well as the theophylline-associated increase in 45Ca levels. Verapamil had no effect on either the fatigue-associated decreases in contractility or the fatigue-enhanced 45Ca uptake. The results of this study strongly suggest that the enhanced contractility associated with theophylline is related to its influence on cellular calcium metabolism. The elevated level of isotopic calcium measured in fatigued muscle probably represents calcium sequestered in the sarcoplasmic reticulum, the result of cAMP-enhanced Ca-adenosine triphosphatase activity.
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PMID:Theophylline, fatigue, and diaphragm contractility: cellular levels of 45Ca and cAMP. 165 Jul 69

In a previous report on the ontogeny of the ovarian adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase activity during prepubertal development of the rat, we concluded that the 4-fold decline in cAMP-dependent protein kinase activity observed in ovaries of 21- to 23-day-old rats was due to the presence of a heat-labile inhibitor in the ovarian extracts (Hunzicker-Dunn et al., 1984). We developed an assay for this ovarian kinase inhibitor activity that was based on the observation that ovarian cytosol added to an exogenous catalytic subunit of cAMP-dependent protein kinase caused a time-dependent and ovarian cytosol protein concentration-dependent inhibition of exogenous catalytic subunit phosphotransferase activity. The present studies were conducted to evaluate the basis for this catalytic subunit inhibitor present in soluble rat ovarian extracts of prepubertal-aged rats. This inhibitor activity was absent from cytosol extracts of rat corpora lutea, rat liver, rabbit follicles, and rabbit corpora lutea. Inhibitor activity present in rat ovarian cytosol was not attributable to insufficient levels of the phosphorylation substrate Kemptide. Inhibitor activity was also not related to the presence of the large amount of catalytic subunit-free regulatory subunit of the cAMP-dependent protein kinase present in ovarian extracts of late juvenile-aged rats. Inhibitor activity, however, did correlate with an endogenous adenosine triphosphatase (ATPase) activity that reduced assay ATP concentrations below levels needed to accurately measure phosphotransferase activity, despite the presence of sodium fluoride (an ATPase inhibitor) and ATP concentrations 5- to 15-fold greater than the Km of the kinase for ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of soluble ovarian adenosine 3',5'-monophosphate-dependent protein kinase activity during prepubertal development in the rat. II. Evaluation of the catalytic subunit inhibitor activity. 252 67

Calcium-activated myosin adenosine triphosphatase (ATPase) activity has been measured in sections of rat ventricles that were rapidly frozen to preserve the structure and regulatory state of myosin occurring in vivo. These results were related to myosin isozyme composition measured in ventricles by native gel electrophoresis and by quantitative immunocytochemistry. Both total ATPase activity and percent alpha-heavy chain rapidly rise during the first month following birth. However, ATPase activity remains constant at a high level from 1 to 12 months following birth, even though percent alpha-heavy chain declines during this period. The ATPase activity of V1 myosin was specifically determined using sections in which V3 myosin had been completely inhibited by exposure to alkaline pH in the absence of adenosine 5'-triphosphate (ATP). Relative V1 specific activity, taken as the ratio of V1 ATPase activity to percent alpha-heavy chain, doubles in the first 2.0 months after birth and then remains approximately constant at this higher level until at least 4 months after birth. The specific activity of V1 can be further increased by the addition of adenosine-3',5'-cyclic monophosphate (cAMP). This effect of cAMP is age dependent, increasing threefold between 1 and 2 months following birth and then declining as V1 is replaced by V3.
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PMID:cAMP regulation of myosin ATPase activity in the maturing rat heart. 282 92

These in vitro studies of golden hamster sperm were undertaken to determine whether: Na+, K+-adenosine triphosphatase (ATPase) activity is required for capacitation; Na+, K+-ATPase activity is altered during capacitation; and cyclic nucleotides can control this enzyme activity. Hamster sperm were incubated in a medium in which capacitation occurred in an asynchronous manner and in which acrosome reactions began to occur after approximately 3.5 h of incubation. Inhibition of the hamster sperm acrosome reaction by the Na+, K+-ATPase inhibitor ouabain (1 microM) added at Time (T) = 2 or T = 3 h could be fully reversed by the addition of the ionophore nigericin (0.1 microM) at T = 3.5 h. However, when ouabain was added at T = 0 or T = 1 h, similar nigericin addition could not completely reverse the inhibition. Na+, K+-ATPase activity of hamster sperm increased by 2 h of incubation (compared to that measured initially after 15 min) and this activity remained elevated at 3.5 h. Addition of either monobutyryl cyclic adenosine 3':5'-monophosphate ( BtcAMP ) (12.9 microM) or monobutyryl cyclic guanosine monophosphate ( BtcGMP ) (10.5 microM), or the phosphodiesterase inhibitor SQ20009 (10 microM) at 2 h produced a stimulation of acrosome reactions at 4 and 5 h. However, while BtcGMP and SQ 20009 also induced a further increase in Na+, K+-ATPase activity measured at 3.5 h, BtcAMP had no effect. Intracellular cAMP and cGMP levels measured showed cAMP increased by 2 h and remained elevated when measured at 3.5 h, while cGMP could not be consistently detected at 15 min, 2 h or 3.5 h. However, assays of high numbers of uncapacitated sperm did detect a low level of cGMP. These results suggest that Na+, K+-ATPase activity increases in and is essential for early capacitation [and thereby eventually for the acrosome reaction (AR)] of hamster sperm and that the increase in Na+, K+-ATPase activity occurring during capacitation is probably mediated by intracellular cGMP but not cAMP, although both cyclic nucleotides stimulate the hamster sperm AR.
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PMID:Hamster sperm Na+, K+-adenosine triphosphatase: increased activity during capacitation in vitro and its relationship to cyclic nucleotides. 632 71

The activity of the Na+/H+ exchanger was studied by measuring the effects of intracellular pH (pHi) and extracellular Na+ [(Na+)o] on pHi recovery and 22Na uptake in rat adipocytes. The resting pHi was acidified from 7.30 +/- 0.02 to 6.99 +/- 0.01 with nigericin in the absence of (Na+)o. pHi recovery induced by 30 mM NaCl was blocked by 100 microM amiloride. The reversibility of the exchanger was studied by Na+ loading, which raised the pHi from 7.30 +/- 0.02 to 7.50 +/- 0.01, and by removing (Na+)o, which decreased pHi to 6.97 +/- 0.01. Both functions of the exchanger, forward and backward, were inhibited by amiloride. The Na+/H+ exchanger was inactive at pHi higher than 7.1 and became increasingly active as pHi decreased to 6.2 (22Na+ uptake, 0.029 +/- 0.003 vs. 0.155 +/- 0.009 nmol/10(5) cells.2.5 min; P < 0.001); this 5-fold stimulation was largely abolished by amiloride (0.025 +/- 0.002; P < 0.001). Na+ influx was also increased as a function of (Na+)o, with an apparent Km of 35 mM. Respective 5- and 44-fold stimulations at 5 mM (0.135 +/- 0.007) and 140 mM (Na+)o (1.228 +/- 0.046 nmol/10(5) cells.2.5 min; P < 0.001) were inhibited by ethylisopropylamiloride. Isoproterenol (Iso; 100 nM) and agents that stimulate cAMP production, such as forskolin (10 microM) and theophyline (1 mM), inhibited the activity of amiloride-sensitive 22Na+ uptake by 85%. Iso inhibited the Na+/H+ exchanger, without affecting the Na+/K(+)-adenosine triphosphatase-dependent and the Na+/K+/Cl- cotransport mechanisms. (Bu)2cAMP (1 mM), a membrane-permeant cAMP analog, mimicked the effects of Iso on the exchanger. The inhibitory effect of Iso was blocked by propranolol, but not by metoprolol, a beta 1-antagonist. In addition, the alpha-adrenergic agonists, phenylephrine (alpha 1) and clonidine (alpha 2), and the alpha-antagonists, prazocin (alpha 1) and yohimbine (alpha 2), did not prevent Iso-induced inhibition of the exchanger. In conclusion, rat adipocytes possess a reversible Na+/H+ exchange mechanism, which is activated by low pHi and normal (Na+)o and is inhibited by Iso via a beta 2-adrenergic receptor stimulation and a cAMP-dependent mechanism.
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PMID:Activation of the Na+/H+ exchanger by cellular pH and extracellular Na+ in rat adipocytes; inhibition by isoproterenol. 778 40

Ca(2+)-mobilizing and cAMP-dependent hormones rapidly increase sodium, potassium-dependent adenosine triphosphatase (Na+/K(+)-ATPase)-mediated transport in rat hepatocytes. To explore the possible role of protein phosphatases in these responses we used a protein phosphatase inhibitor, okadaic acid. Okadaic acid stimulation of ouabain-sensitive 86Rb(+)-uptake was maximal between two and three minutes and displayed an EC50 of 41 +/- 1 nM. Inhibition of Na+/H+ exchange with an amiloride analog abolished the response to insulin, but had no effect on okadaic acid-mediated stimulation of Na+/K(+)-ATPase transport. In hepatocytes metabolically-radiolabeled with 32Pi, okadaic acid stimulated the incorporation of radioactivity into several 95 kDa peptides, one of which reacted with anti-LEAVE peptide antisera, that recognizes Na+/K(+)-ATPase alpha-subunits. In other experiments Na+/K(+)-ATPase was immunoprecipitated from detergent-solubilized membrane fractions of metabolically-radiolabeled cells with an antisera to purified rat kidney Na+/K(+)-ATPase. A 95 kDa phosphoprotein was immunoprecipitated using anti-Na+/K(+)-ATPase antisera, but not by preimmune serum. Okadaic acid stimulated incorporation of radioactivity into this band by 220 +/- 28%. These findings provide support for the hypothesis that rapid stimulation of hepatic Na+/K(+)-ATPase by hormones may be related to protein kinase/phosphatase-mediated changes in the phosphorylation state of the Na+/K(+)-ATPase alpha-subunit.
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PMID:Okadaic acid stimulates ouabain-sensitive 86Rb(+)-uptake and phosphorylation of the Na+/K(+)-ATPase alpha-subunit in rat hepatocytes. 798 91

A study was carried out to investigate the short-circuit current (Isc) response to noradrenaline (NA) and the signal transduction mechanisms involved in cultured rat cauda epididymal epithelium. In normal Krebs-Henseleit solution, NA (10 mumol.l-1) added basolaterally elicited a biphasic Isc response consisting of a transient spike followed by a second sustained response. The biphasic response was almost abolished by removing ambient Cl-. Preloading the tissues with a cell-permeant Ca2+ chelator, 1,2-bis(2-aminophenoxy) ethane-N,N,N',N',-tetraacetic acid acetoxymethyl ester (BAPTA/AM), or pretreating them with thapsigargin (Tg), a microsomal adenosine triphosphatase inhibitor abolished the initial spike in the Isc response to NA, but had little effect on the second component. Pretreating the tissues with a non-selective beta-antagonist, nadolol, reduced the second Isc response in a dose-dependent fashion but the initial spike was not affected. Microfluorimetric studies showed that NA (100 mumol.l-1) elicited single Ca2+ spikes in isolated epididymal cells, which could be abolished by prior treatment with Tg. Biochemical assays showed that NA (10 mumol.l-1) increased intracellular cyclic adenosine monophosphate concentration ([cAMP]i) and the response was abolished by prior treatment with nadolol (50 mumol.l-1). The results showed that NA elicited a biphasic Isc response mediated by a rise in intracellular Ca2+ concentration ([Ca2+]i) followed by a rise in [cAMP]i. The Ca(2+)-mediated Isc response had a faster onset and more transient action than the cAMP counterpart. It is suggested that NA released from noradrenergic nerve endings regulates transepithelial Cl- secretion in the epididymis thereby providing the specialized millieu vital for sperm storage and maturation.
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PMID:Biphasic short-circuit current response to noradrenaline mediated by Ca2+ and cAMP in cultured rat epididymal epithelium. 801 89

The effect of long-term treatment with propafenone, metoprolol and amiodarone was studied on the activity of Na,K-adenosine triphosphatase in lymphocytes and the plasma level of cAMP in patients with ventricular arrhythmias. The investigations were carried out in 86 patients with cardiac dysrhythmias caused by coronary artery disease, hypertension, post-inflammatory and alcohol cardiomyopathy and preexcitation syndrome. Propafenone was used in treatment in 31 patients, metoprolol in 30, amiodarone in 25. The activity of of Na,K-adenosine triphosphatase in lymphocytes was estimated by the method of Heagerty et al. The plasma level of cAMP was measured radioimmunologically. Disappearance of ventricular arrhythmias after treatment was accompanied by increase in activity of of Na,K-adenosine triphosphatase and decrease in plasma level of cAMP regardless of which drug was used. Ineffective treatment did not affect both parameters.
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PMID:[The effect of treatment with propafenone, metoprolol and amiodarone on lymphocyte sodium efflux and level of cAMP in serum]. 852 94

Thyroid hormone exerts predictable effects on the contractile performance of the heart in part by regulating the transcription of genes encoding specific calcium transporter proteins. In a rat model of hypothyroidism, left ventricular (LV) contractile function as measured by ejection fraction was decreased by 22% (P < 0.05), and this was returned to control values with T3 treatment. In confirmation of prior studies, LV phospholamban (PLB) protein content was significantly decreased by 25% and 40% compared with hypothyroid LV when the animals were treated with T3 at two doses, 2.5 and 7.0 microg/day, respectively. The ratio of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2) to PLB protein content was thus increased by 171% and 207%, respectively (P < 0.01). Resolution of the phosphorylated PLB pentamers by SDS-PAGE showed that T3 infusion at 2.5 and 7.0 microg/day decreased (P < 0.001) the amount nonphosphorylated pentamers by 82% and 95%, respectively, in a dose-dependent manner. T3 treatment produced an increase in the proportion of highly phosphorylated PLB pentamers (more than five phosphates) when expressed as a fraction of total pentameric molecules (P < 0.05). Site-specific antibodies showed that the T3-induced increase in phosphorylated PLB pentamers was the result of an increase in both serine 16 and threonine 17 phosphorylation. We conclude that thyroid hormone, in addition to regulating the expression of cardiac PLB, is able to alter the degree of PLB phosphorylation, which correlates with enhancement of LV contractile function. These studies suggest that T3 may augment myocyte calcium cycling via changes in both cAMP- and calcium/calmodulin-dependent protein kinase activities.
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PMID:Thyroid hormone regulation of phospholamban phosphorylation in the rat heart. 1083 Mar 1


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