Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Calcium transporting systems and the regulatory events accompanying them are pivotal in the function of the cardiac cell. The concerted involvement of the various membranes achieve cellular calcium homeostasis that can also respond to the physiological exigencies of the cell. Three membrane systems are primarily involved; the sarcolemma, sarcoplasmic reticulum, and the mitochondria. The various Ca2+ transport systems that have been described in these membranes are as follows: the calcium channel, Ca2+-ATPase, Ca2+-Mg2+ ATPase, and sodium-calcium exchanger in the sarcolemma; the Ca2+-Mg2+ ATPase and a possible calcium channel in the sarcoplasmic reticulum; and the sodium-calcium exchanger and electrophoretic calcium uniporter in the mitochondrial inner membrane. These systems mediate calcium fluxes to maintain physiological cytosolic calcium concentrations. beta-Adrenergic hormones regulate calcium transport systems in sarcolemma and sarcoplasmic reticulum, while alpha-adrenergic hormones modulate those in the mitochondria and probably in the sarcolemma. The response to these hormones is initiated at the sarcolemma, which contains the specific receptors. Intracellularly the effects are propagated by secondary messengers, e.g., cAMP, calcium, and lipid changes. Specific proteins are also involved in these events. Phospholamban, a 22 000 dalton protein, is involved in mediating the cAMP-dependent inotropic effects, by activating the Ca2+-Mg2+ ATPase of the sarcoplasmic reticulum. Alterations in any one of the systems involved in the regulation of calcium transport or in the calcium transport systems per se, would then result in drastic alterations in the cellular calcium homeostasis. Such effects could be of significance in cellular dysfunction during cardiac disease.
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PMID:Regulation of calcium transport in cardiac cells. 614 3

In isolated and enriched guinea pig parietal cells the inhibitory effects of the calcium channel antagonists verapamil and gallopamil on 14C-aminopyrine uptake (= H+ secretion) have been analyzed. Both verapamil and gallopamil inhibit acid secretion in a concentration-dependent manner with an IC50 of 12.1 and 10.9 mumol/l respectively. The type of inhibition is noncompetitive in nature. Verapamil inhibits the acid response to histamine, dibutyryl-cAMP, and KCl with IC50 values not significantly different from each other. Exposure of the cells to verapamil and subsequent washing enhances the acid response to histamine for an unknown reason. It is concluded that the calcium channel antagonists verapamil and gallopamil inhibit acid secretion in vitro by interfering with the parietal cell proton pump, the K+/H+-ATPase.
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PMID:Calcium channel antagonists verapamil and gallopamil are powerful inhibitors of acid secretion in isolated and enriched guinea pig parietal cells. 631 Jun 46

The ability of a calcium channel blocker (D-600) and a beta-adrenergic antagonist (propranolol) to modify the chemical, biochemical, functional, and ultrastructural manifestations of reperfusion injury following circumflex coronary artery ligation has been examined using an open chest, anaesthetized rabbit model of acute myocardial ischaemia. A 40-min ligation period followed by 60 min of reperfusion produced a decrease in mitochondrial azide-sensitive ATPase activity which could be prevented by pretreatment with either agent. While both drugs caused an equivalent (approximately 50%) reduction in myocardial Ca2+ accumulation associated with reperfusion, only D-600 preserved Mg2+ and Na+ levels. The greater protective effects of D-600 on sarcolemmal integrity were also apparent from its superior ability (when compared with propranolol) to offer protection against the loss of sarcolemmal Na+-K+ ATPase activity which we have previously suggested may parallel the development of irreversible ischaemic injury. Further support for these biochemical data came from ultrastructural studies in which we demonstrated significant improvement in subcellular membrane integrity by both of the drugs. In contrast to the foregoing protective actions, D-600 and propranolol failed to prevent the marked decrease in myocardial contractile function and in cellular ATP content associated with reperfusion. The superior effectiveness of D-600 in our system cannot be explained on the basis of Ca2+ antagonism alone, but is more likely a result of its greater negative inotropism.
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PMID:The protective effects of D-600 and propranolol on reperfusion injury in the anaesthetized rabbit. 632 79

We have investigated the effects of veratridine, a Na+ channel activator, and ouabain, an inhibitor of Na+-K+-ATPase, on short term (1-h) PRL release from primary cultures of rat anterior pituitary cells and from the rat anterior pituitary cell line GH4C1 in culture. Both compounds should increase intracellular Na+. Veratridine (20-500 microM) and ouabain (0.1-3 mM) stimulated PRL release from normal cells. The stimulation was inhibited by the omission of Ca++ from the release buffer or by preincubation with the calcium channel blocker D600 (20-500 microM), suggesting a role for Ca++ in the action of these compounds. Ouabain (1 mM), but not veratridine (200 microM), stimulated PRL release from GH4C1 cells, an effect that was also inhibited by calcium channel blockers. In the presence of the dopaminergic agonist bromocriptine (30 nM), the amount of stimulated release by veratridine (200 microM) and ouabain (1 mM) was reduced by 50%. The veratridine effect was only partially inhibited by preincubation of the cells with the Na+ channel blocker tetrodotoxin (1 and 10 microM), but the effect was inhibited completely when Na+ in the buffer was replaced by choline, suggesting that the action of veratridine requires extracellular Na+. The results of this study indicate that 1) ouabain- and veratridine-stimulated PRL release are largely dependent on Ca++; 2) veratridine appears to act through a tetrodotoxin-insensitive mechanism; and 3) stimulation of PRL release by these compounds is similar to that by 50 mM KCl and cAMP in its sensitivity to bromocriptine.
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PMID:Veratridine and ouabain stimulate calcium-dependent prolactin release. 661 70

We have tested the hypothesis that altered vascular reactivity, specifically the appearance of spontaneous and BayK 8644 (L-type voltage gated calcium channel agonist)-induced oscillations in the carotid artery and the sarcoplasmic reticulum Ca(2+)-ATPase inhibitor cyclopiazonic acid (CPA)-induced oscillations in the aorta from stroke-prone spontaneously hypertensive rats (SHRS), are dependent upon angiotensin II production early in life. SHRSP and normotensive Wistar-Kyoto (WKY) rats were treated from 6-10 weeks of age with vehicle, hydralazine/hydrochlorothiazide (used as a control for lowered blood pressure) or the angiotensin converting enzyme inhibitor ramipril (3 mg/kg/day). Systolic blood pressures were measured weekly in rats from 6 to 17 weeks of age. In SHRSP (at 17 weeks of age), ramipril-treatment but not hydralazine/hydrochlorothiazide attenuated the long term expression of elevated systolic blood pressure in adult SHRSP while blood pressures of all adult WKY rats were unaffected by any treatment. At 17 weeks, rats were killed and arteries removed for in vitro measurement of isometric contractile activity. Only the incidence of spontaneous oscillations (carotid artery) was affected by ramipril treatment; ramipril did not change the frequency of BayK 8644-induced oscillations in the artery or the frequency of CPA-induced oscillations in aorta from either SHRSP or WKY. These data indicate that while spontaneous oscillations in the carotid artery may be dependent on an angiotensin II-sensitive mechanism during development, agonist-induced oscillations (CPA and BayK 8644) appear not to be angiotensin II-dependent. Thus, not all of the contractile oscillations which appear in vascular smooth muscle from SHRSP are angiotensin II-dependent, suggesting that some of these vascular abnormalities may develop at a time separate from that in which increased blood pressure is firmly established and may not be associated with the for maintenance of elevated blood pressure.
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PMID:Effects of ramipril on contractile oscillations in arteries from genetically hypertensive rats. 753 66

We performed experiments to elucidate the calcium influx pathways in freshly dispersed rabbit corneal epithelial cells. Three possible pathways were considered: voltage-gated Ca++ channels, Na+/Ca++ exchange, and nonvoltage-dependent Ca(++)-permeable channels. Whole cell inward currents carrying either Ca++ or Ba++ were not detected using voltage clamp techniques. We also used imaging technology and the Ca(++)-sensitive ratiometric dye fura 2 to measure changes in intracellular Ca++ concentration ([Ca]i). Bath perfusion with NaCl Ringer's solution containing the calcium channel agonist Bay-K-8644 (1 microM), or Ni++ (40 microM), a blocker of many voltage-dependent calcium channels, did not affect [Ca++]i. Membrane depolarization with a KCl Ringer's bath solution resulted in a decrease in [Ca++]i. These results are inconsistent with the presence of voltage gated Ca++ channels. Nonvoltage gated Ca++ entry, on the other hand, would be reduced by membrane depolarization and enhanced by membrane hyperpolarization. Agents which hyperpolarize via stimulation of K+ current, such as flufenamic acid, resulted in an increase in ratio intensity. The cells were found to be permeable to Mn++ and bath perfusion with 5 mM Ni++ decreased [Ca++]i suggesting that the Ca++ conductance was blocked. These results are most consistent with a nonvoltage gated Ca++ influx pathway. Finally, replacing extracellular Na+ with Li+ resulted in an increase in [Ca++]i if the cells were first Na(+)-loaded using the Na+ ionophore monensin and ouabain, a Na(+)-K(+)-ATPase inhibitor. These results suggest that Na+/Ca++ exchange may also regulate [Ca++]i in this cell type.
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PMID:Calcium entry in rabbit corneal epithelial cells: evidence for a nonvoltage dependent pathway. 754 Oct 85

Resistance of tumors to a variety of chemotherapeutic agents presents a major problem in cancer treatment. The gene responsible for multidrug resistance, termed mdr1, encodes a membrane glycoprotein (P-glycoprotein) that acts as a pump to transport various cytotoxic agents. The P-glycoprotein has been shown to bind anticancer drugs and several resistance-reversing agents including calcium channel blockers, and to be an ATPase. The P-glycoprotein was found to function in the blood-brain barrier. The physiological function of the P-glycoprotein in relation to therapy is discussed.
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PMID:[Mechanism of resistance to antitumor agents--its involvement in blood-brain barrier]. 756 98

The kidneys play a vital role in mineral homeostasis. In this review, the handling of calcium and the methods currently applied to measuring its intracellular concentration are discussed. The bulk of calcium absorption proceeds in proximal tubules, with smaller fractions recovered by thick ascending limbs, distal convoluted tubules, and connecting tubules. Hormonally regulated transcellular calcium absorption is essentially limited to distal convoluted and connecting tubules. At physiological concentrations, parathyroid hormone, calcitonin, and vitamin D increase net calcium absorption. Calcium absorption by polarized epithelial cells is a two-step process wherein calcium enters the cell across apical plasma membranes and exits across basolateral membranes. Recent electrophysiological and pharmacological experiments demonstrate that apical entry is mediated by calcium channels, which are modestly calcium selective, sensitive to dihydropyridine-type calcium channel blockers, and exhibit a wide range of single-channel conductances. Cellular calcium efflux is mediated by Ca(2+)-ATPase and by Na+/Ca2+ exchange. Ca(2+)-ATPase activity is highest in segments that exhibit significant rates of active calcium absorption. Multiple plasma membrane Ca(2+)-ATPase isoforms have been found in the kidney. Several renal Na+/Ca2+ exchange isoforms have been identified, and their role in effecting calcium efflux is under investigation.
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PMID:Cellular calcium transport in renal epithelia: measurement, mechanisms, and regulation. 762 90

Mononuclear cell infiltration and local cytokine elaboration are hallmarks of inflammatory and immunologic heart diseases. To test the hypothesis that cytokines can modulate cardiac myocyte growth and phenotype, myocytes cultured from neonatal rat hearts were exposed to IL-1 beta, an inflammatory cytokine prevalent in myocardial inflammation. IL-1 beta (2 ng/ml, 24 h) increased [3H]leucine incorporation by 30 +/- 4% (P < 0.001, n = 29) and net cellular protein content by 20 +/- 4% (P < 0.001, n = 27), but had no effect on DNA synthesis. Northern hybridization showed that IL-1 beta increased prepro-atrial natriuretic factor (ANF) mRNA (5.8 +/- 1.5-fold, P < 0.01, n = 13) and beta-myosin heavy chain (beta-MHC) mRNA (> 10-fold, n = 4), and decreased mRNA levels for sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) (-46 +/- 7%; P < 0.001; n = 11), calcium release channel (CRC) (-65 +/- 11%, P < 0.001, n = 8) and voltage-dependent calcium channel (VDCC) (-53 +/- 7%, P < 0.001, n = 8). NG-monomethyl-L-arginine (1 mM), an inhibitor of nitric oxide (NO) synthesis, did not inhibit the IL-1 beta-induced protein synthesis or changes in mRNA levels. In ventricular myocardium obtained from adult rats treated with lipopolysaccharide (4 mg/kg intraperitoneally 18 h) to stimulate systemic cytokine production, there were changes in the mRNA levels for beta-MHC (6 +/- 1-fold, P < 0.01, n = 4), SERCA2 (-65 +/- 4%, P < 0.0001, n = 4), CRC (-67 +/- 5%, P < 0.001, n = 4), and VDCC (-58 +/- 5%, P < 0.001; n = 4) that were qualitatively similar to those observed in cultured myocytes. Thus, IL-1 beta, acting via an NO-independent mechanism, caused myocyte hypertrophy associated with induction of fetal genes (ANF and beta-MHC) and downregulation of three important calcium regulatory genes (SERCA2, CRC, and VDCC). IL-1 beta may contribute to the abnormal structural and functional alterations of cardiac myocytes in conditions marked by mononuclear cell infiltration.
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PMID:Interleukin-1 beta modulates the growth and phenotype of neonatal rat cardiac myocytes. 763 44

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


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