Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Smooth muscle cells contain two distinct Ca2+-transport ATpases with a different subcellular localization. The plasmalemmal Ca2+ pump has a relative molecular weight (Mr) of 140k and its phospho-intermediate level is increased by La3+. Its resemblance to the erythrocyte Ca2+ pump is further confirmed by its calmodulin-binding capacity and its antigenic properties. A 100k Ca2+-transport ATPase is localized in the endoplasmic reticulum. Its phospho-intermediate level is decreased by La3+, and it is antigenically related to the cardiac sarcoplasmic reticulum Ca2+-transport ATPase. These two different Ca2+-transport ATPases are present in both visceral and vascular smooth muscle, but tissue- and species-dependent differences in their relative amount have been observed. The endoplasmic-reticulum Ca2+-transport ATPase is regulated via phospholamban. Phosphorylation of this regulatory protein by cAMP-dependent as well as by cGMP-dependent protein kinase stimulates the endoplasmic-reticulum Ca2+ pump. The activity of the plasmalemmal Ca2+-transport ATPase can be modulated by calmodulin, negatively charged phospholipids, and by receptor-binding agonists. cGMP-dependent protein kinase also exerts a stimulatory effect on the plasmalemmal Ca2+ pump, but this effect is not mediated via a direct phosphorylation of the Ca2+ pump.
J Cardiovasc Pharmacol 1988
PMID:The (Ca2+-Mg2+)-ATPases of the plasma membrane and of the endoplasmic reticulum in smooth muscle cells and their regulation. 246 79

The biochemical and functional similarities between skeletal muscle sarcoplasmic reticulum and the microsomal Ca2+ store of nonmuscle cells are discussed. It is shown that antibodies raised against two characteristic proteins of sarcoplasmic reticulum, Ca2+ ATPase and calsequestrin, recognize similar proteins in nonmuscle cells. The subcellular distribution of these two antigens was studied at the subcellular levels in ultrathin cryosections. In a variety of cell types these two proteins were found to be localized in small membrane enclosed vesicles, apparently distinct from other known organelles. We propose that these newly recognized structures (calciosomes) represent the functional equivalent of sarcoplasmic reticulum in nonmuscle cells.
J Cardiovasc Pharmacol 1988
PMID:Immunocytological identification of the microsomal calcium store of nonmuscle cells. 246 83

Epinephrine-induced hypokalemia appears to be mediated by beta 2-agonist activation of Na+/K+ ATPase. To determine whether dopamine and dobutamine induce hypokalemia, eight adult mongrel dogs were anesthetized and studied in random crossover fashion. Potassium [K+] was measured with an ion-selective microelectrode, and central hemodynamics were measured continuously. After stabilization, dopamine and dobutamine were infused at doses of 2, 4, 8, and 20 micrograms/kg/min (15-min increments/dose), and 0.9% NaCl was infused at equivalent volumes, with a 1-h washout between treatments. The mean change in [K+] at each infusion rate was compared between treatments among dogs with an adequate hemodynamic response. Among dopamine responders (n = 5), [K+] decreased from 3.74 +/- 0.42 mEq/L at baseline to 3.63 +/- 0.51 at 2 micrograms/kg/min (p less than 0.02) and was not significantly different at higher doses. Among dobutamine responders (n = 7), [K+] decreased from 3.52 +/- 0.74 at baseline to 3.31 +/- 0.87 at 8 micrograms/kg/min (p less than 0.02) and 3.25 +/- 0.86 at 20 micrograms/kg/min (p less than 0.02), and was not significantly different at lower doses. We conclude that dopamine and dobutamine induce significant hypokalemia, consistent with their adrenergic agonist activity, and this may be related to the known arrhythmogenicity of these agents.
J Cardiovasc Pharmacol 1989 Apr
PMID:Dopamine and dobutamine induce hypokalemia in anesthetized dogs. 247 Oct 6

The role of structural features of sulmazole, an imidazo(4,5-b)pyridine, in its inotropic action was examined by comparison with its reduced (4-methylthiophenyl) analog EMD 46512 and the corresponding imidazo(4,5-c)pyridine isomers isomazole and EMD 41000 on isolated guinea-pig papillary muscles and right atria and on Na,K-ATPase and phosphodiesterase III isolated from guinea-pig hearts. The pyridine nitrogen position in sulmazole was crucial for affinity to Na,K-ATPase (IC50 = 350 microM) because the imidazo(4,5-c)pyridines had little effect. Participation of Na,K-ATPase inhibition in sulmazole's inotropic effect (EC50 = 180 microM) was suggested by synergism with the Na channel activator germitrine. The methylsulfinyl oxygen at the phenyl ring decreased the affinity to Na,K-ATPase of sulmazole 40-fold: The reduced analog EMD 46512 was a potent inhibitor of Na,K-ATPase (IC50 = 8.5 microM) and a more potent inotropic agent (EC50 = 8.2 microM) that appeared to act predominantly through Na,K-ATPase inhibition. Micromolar through Na,K-ATPase inhibition. Micromolar IC50s for inhibition of phosphodiesterase III were 49 (sulmazole), 34 (EMD 46512), 18 (isomazole), and 13 (EMD 41000). Participation of this mechanism in the inotropic effect of sulmazole, isomazole, and EMD 41000, but not EMD 46512, was indicated by augmentation of slow action potentials, synergism with histamine, inhibition by carbachol, and (with the exception of EMD 41000) a positive chronotropic effect on the right atrium. Sulmazole appeared to combine the actions of its 4-methylthiophenyl analog EMD 46512 (an inhibitor of Na,K-ATPase) and of its imidazo(4,5-c)pyridine isomer isomazole (an inhibitor of phosphodiesterase III).
J Cardiovasc Pharmacol 1989 May
PMID:Imidazopyridines: roles of pyridine nitrogen position and methylsulfinyl oxygen for in vitro positive inotropic mechanism and chronotropic activity. 247 14

We have studied the effect of pimobendan (UD-CG 115 BS) on the electrical, mechanical, and biochemical activity of intact and detergent-skinned preparations of cardiac muscle. Racemic pimobendan increased the contractile force of guinea pig papillary muscle preparations and this positive inotropic action was associated with potentiation of the Ca2+-dependent slow action potentials (APs). However, in the presence of 25 mM [K]0 and maximally activating concentrations of isoproterenol, isometric force was increased further by addition of 50 microM pimobendan with no effect on the slow action potential. Experiments with chemically skinned heart muscle fibers showed that pimobendan, in a dose-dependent manner, increased active tension developed at submaximally activating concentrations of Ca2+. The tension-cost (unit increase in ATPase rate/unit increase in force) was unchanged in the presence of pimobendan. Force-pCa and ATPase-pCa relations of skinned fiber preparations contracting isometrically were shifted to the left by 0.15-0.20 pCa units in the presence of 50 microM pimobendan. The mechanism for this effect was shown to be an increase in the Ca affinity of the regulatory binding sites of troponin C (TNC). These effects are due mainly to the l optical isomer of pimobendan. Addition of either the d or l isomer of pimobendan to preparations. maximally stimulated by 1 microM isoproterenol, did not affect the slow AP parameters, but did increase contractile force to 124% of control by the d isomer and to 184% of control by the l isomer. The Ca2+-sensitizing effect of l-pimobendan on skinned fiber preparations was substantially greater than that of the d isomer.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1989
PMID:The positive inotropic effect of pimobendan involves stereospecific increases in the calcium sensitivity of cardiac myofilaments. 247 95

In response to increasing demand, the cardiac muscle has developed several adaptational mechanisms. Gene expression is modified in a quantitative and a qualitative way since the heart hypertrophies and since its structure changes to improve the efficiency of the contraction. The sarcomere modifications are both species- and tissue-specific. An isoenzymic shift of myosin from high adenosine triphosphatase (ATPase) activity form V-1 to low activity form V-3 occurs in all conditions in which V-1 is initially predominant, i.e., in rat (and also rabbit) ventricles and the atria of other species, including humans. It was not observed in conditions in which V-3 was predominant, as in human ventricles (and also in those of cats and pigs). Another shift from creatine kinase (CK) monomer M to CK B, the form that predominates in the fetal heart, is also observed. The sarcolemma is also modified, at least in rats. The digitalis receptor was characterized by studying the inotropic effect of the drug on an isolated heart preparation and on a purified preparation of sarcolemma with a high Na+,K(+)-ATPase activity by binding [3H]ouabain and ouabain-induced inhibition of the enzymatic activity. In hypertrophied heart, both the recovery of normal contractility after ouabain infusion and the release of previously bound ouabain infusion and the release of previously bound ouabain were slowed, as for fetal hearts. Changes in other inotropic receptors have also been reported. From a practical point of view, this means that screening of new inotropic agents has to be done on hypertrophied hearts and not, as usual, on normal tissue.
J Cardiovasc Pharmacol 1987
PMID:Adaptational changes of sarcomere and sarcolemma during chronic cardiac overloading in rats and in humans. 248 18

The metabolic pattern of aortic vein grafts in rats was studied by estimating histochemically the activity of the hydrolytic enzymes alfa-esterase, aminopeptidase, adenosine triphosphatase, acid phosphatase and alkaline phosphatase. The enzyme activity was lowest in the 16 hour and 1 day old grafts, and recovery was noted at three days. Five days after transplantation the enzyme activities were higher than in the non-transplanted veins. The rapid increase in enzymatic activity found in histochemical studies on wound healing was not seen in these vein grafts. At four weeks some grafts showed intimal thickening the activity of which did not exceed that of the other layers of the graft wall. At the end of the observation period of sixteen weeks most of the grafts showed intimal thickening, and this layer stained intensely especially for ATPase. The staining pattern of most of the grafts at sixteen weeks resembled that of the aortic media.
J Cardiovasc Surg (Torino)
PMID:Assessment of metabolic activity in aortic vein grafts in rats by histochemical examination of hydrolases. 252 49

Hamsters fed a Mg-deficient diet (MD) develop a cardiomyopathy (CM) with foci of myocardial necrosis, calcification, and modest mononuclear and giant cell infiltration. We hypothesize that the lesions are secondary to Ca overload following an increase in myocardial Na due to inhibition of (Na.K)-ATPase and secondary Na-Ca exchange. Nifedipine and digoxin were selected as agents to test this hypothesis. Hamsters were given nifedipine, digoxin, or placebo as sustained release subcutaneous pellets the same day they were started on the MD diet. Animals were killed after 14 days, and MD lesions were quantified in H&E stained slides. Regression analysis showed that nifedipine produced a dose-dependent reduction in lesion abundance (p less than .005) and diameter (p less than .05), while digoxin produced a dose-dependent increase in lesion abundance (p less than .005) and diameter (p less than .005). These results support the hypothesis that MDCM is secondary to Ca overload coupled to inhibition of (Na.K)-ATPase of cardiac myocytes.
Am J Cardiovasc Pathol 1989
PMID:Sodium pump and calcium channel modulation of Mg-deficiency cardiomyopathy. 255 52

Age-associated ouabain sensitivity was investigated in isolated perfused guinea pig heart and the findings were correlated with its receptor function. Ouabain (0.1 mumol L-1) produced average positive inotropic responses of 22% in 15-day-old, 25% in 4-6 month-old, and 34% in 18-24-month-old guinea pig hearts. The time required to produce the greatest positive inotropic response was 28 min in 15-day- to 6-month-old guinea pig hearts and 20 min in 18-24-month-old guinea pig hearts. To cause arrhythmias and cardiac arrest, 2.1 mumol L-1 ouabain was required in age groups of 15 days to 6 months, and 1.2 mumol L-1 in age groups of 12-24 months. The time of onset of arrhythmias and cardiac arrest was also significantly less in older than in younger animals. Cardiac membranes from 12-24-month-old guinea pig hearts had significantly lower Na+, K+ -ATPase activity per mg of sarcolemmal protein and numbers of [3H]ouabain binding sites than those from 28-day- to 6-month-old hearts. The enzyme inhibition by 0.1 mumol L-1 ouabain was, however, less in younger than in older groups. The difference in the inhibition of enzyme was reflected in lower ouabain binding affinity (Kd) in younger animals. The data confirm the existence of an age-related difference in ouabain sensitivity and suggest that these differences may be due to changes in receptor function.
J Cardiovasc Pharmacol
PMID:Mechanisms of age-related differences in the cardiotoxic action of digitalis. 258 Oct 77

To investigate the effect of inhibition of cerebral Na+, K+-ATPase on cardiovascular regulation ouabain was injected into the lateral ventricle or the posterior hypothalamus in either conscious or urethane anaesthetised, deoxycorticosterone-salt hypertensive (DOCA) and sham operated (sham) rats. Ouabain injected intracerebroventricularly produced dose dependent vasopressor responses and tachycardia in the conscious rat; the magnitude of the pressor response was consistently larger in DOCA than in sham rats. In anaesthetised rats the pressor responses were accompanied by corresponding increases in abdominal sympathetic nerve activity. Thus the magnitude of the pressor responses, tachycardia, and the increases in nerve activity was again significantly greater in DOCA than in sham rats. Intrahypothalamic injections of ouabain produced pressor responses that were accompanied by consistent increases in both heart rate and abdominal sympathetic nerve activity in anaesthetised rats. In contrast to the intracerebroventricular injections the percentage increases from baseline blood pressure were significantly greater in sham than in DOCA rats at 5 min after injection. These results indicate that the centrally induced vasopressor response to ouabain, via the periventricular or bulbospinal system or both, is increased in DOCA-salt hypertensive rats whereas the pressor mechanism via the posterior hypothalamus is suppressed in DOCA rats.
Cardiovasc Res 1987 Jun
PMID:Centrally induced vasopressor responses to ouabain in DOCA-salt hypertensive rats. 282 May 76


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>