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)

Angiotensin IV, [[des-Asp1,Arg2]ANG II or ANG-(3-8)], has been shown to preferentially bind to a novel angiotensin binding site (AT4 receptor). The cellular location and function of this receptor in the rat kidney is unknown. Autoradiography localized AT4 receptors to the cell body and apical membrane of convoluted and straight proximal tubules in the cortex and outer stripe of the outer medulla. ANG IV (0.1 pM-1 microM) elicited a concentration-dependent decrease in transcellular Na+ transport (as measured by proximal tubule O2 consumption rates) in fresh suspensions of control or nystatin-stimulated (bypasses rate-limiting step of apical Na+ entry) rat proximal tubules. The inhibitory effect of 1 pM ANG IV was unaltered by either 1 microM losartan (AT1-receptor antagonist) or 1 microM PD-123319 (AT2-receptor antagonist) and yet was abolished by 1 microM divalinal-ANG IV (AT4-receptor antagonist) or ouabain pretreatment. These results demonstrate that the kidney AT4-receptor system is localized to the proximal tubule and suggests that one potential biological role of this system is in the regulation of Na+ transport by inhibiting a ouabain-sensitive component of Na(+)-K(+)-adenosinetriphosphatase activity in the rat.
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PMID:Angiotensin IV AT4-receptor system in the rat kidney. 948 24

Cultured human umbilical vein endothelial cells (HUVECs) at passage 4 specifically bound 70 +/- 12 fmol [3,5-3H]Tyr4-Ile5-angiotensin (Ang) II/mg protein, with a Kd of 0.9 +/- 0.36 nM. Binding was eliminated in cells preincubated with a monoclonal antibody (6313/G2) raised against the subtype AT1 of the Ang II receptor. Freshly seeded HUVECs were positive for 6313/G2 antibody by immunocytochemistry, and such immunoreactivity was still retained at passage 4. Incubation of HUVECs for 20 min with different concentrations of Ang II provoked a significant increment in Na+/K+ ATPase activity compared with controls, in a dose- and time-dependent manner. Maximal response was obtained with 1000 pM Ang II after 20 min stimulation and resulted in a 2.2-fold increment in Na+/K+ ATPase activity. This stimulation was abolished when cells were incubated with 1000 pM Ang II in the presence of 1 microM of the specific AT1 subtype inhibitor, DuP753. Moreover, preincubation of HUVECs with 6313/G2 or with 1 mM dithiothreitol also inhibited the stimulatory effect of Ang II. These results suggest that the AT1 receptor subtype mediates the Na+/K+ ATPase response to Ang II in these cells.
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PMID:Angiotensin II AT1 receptors and Na+/K+ ATPase in human umbilical vein endothelial cells. 948 4

To evaluate whether K depletion enhances in vivo bicarbonate reabsorption (JtCO2) in surviving distal tubules (DT), we compared DT JtCO2 in five-sixths nephrectomized rats (Nx) with and without dietary K depletion (Nx-K). Furthermore, to identify possible mechanisms of increased JtCO2, we perfused inhibitors of proton secretion in both Nx and Nx-K rats. JtCO2 (102 +/- 8 pmol.min-1.mm-1) was significantly increased in Nx-K vs. Nx rats (65 +/- 7 pmol.min-1.mm-1, P < 0.05) but unaffected by 10(-6) M losartan perfusion (94 +/- 6 pmol.min-1.mm-1, P = not significant). Although 10(-5) M Sch-28080 also had no significant effect, 5 x 10(-9) M concanamycin A perfusion significantly decreased JtCO2 in Nx-K rats to 65 +/- 8 pmol.min-1. mm-1 (P < 0.05). Morphometric evaluation and H(+)-ATPase immunogold labeling of Nx-K A-type intercalated cells revealed cellular hypertrophy, elaborated apical microplicae, and enhanced H(+)-ATPase apical polarization. Accordingly, these combined studies confirm that K depletion enhances JtCO2 in surviving DT by stimulating H(+)-ATPase activity, independent of the AT1 receptor.
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PMID:K depletion stimulates in vivo HCO3 reabsorption in surviving rat distal tubules. 957 89

The present study was designed to determine the cellular signaling mechanisms responsible for mediating the effects of angiotensin II on proximal tubular Na+,K+-ATPase activity. Angiotensin II produced a biphasic effect on Na+,K+-ATPase activity: stimulation at 10(-13) - 10(-10) M followed by inhibition at 10(-7) - 10(-5) M of angiotensin II. The stimulatory and inhibitory effects of angiotensin II were antagonized by losartan (1nM) suggesting the involvement of AT1 receptor. Angiotensin II produced inhibition of forskolin-stimulated cAMP accumulation at 10(-13) - 10(-10) M followed by a stimulation in basal cAMP levels at 10(-7) - 10(-5) M. Pretreatment of proximal tubules with losartan (1nM) antagonized both the stimulatory and inhibitory effects of angiotensin II on cAMP accumulation. Pretreatment of the proximal tubules with pertussis toxin (PTx) abolished the stimulation of Na+,K+-ATPase activity but did not affect the inhibition of Na+,K+-ATPase activity produced by angiotensin II. Pretreatment of the tubules with cholera toxin did not alter the biphasic effect of angiotensin II on Na+,K+-ATPase activity. Mepacrine (10microM), a phospholipase A2 (PLA2) inhibitor, reduced only the inhibitory effect of angiotensin II on Na+,K+-ATPase activity. These results suggest that the activation of AT1 angiotensin II receptors stimulates Na+,K+-ATPase activity via a PTx-sensitive G protein-linked inhibition of adenylyl cyclase pathway, whereas the inhibition of Na+,K+-ATPase activity following AT1 receptor activation involves multiple signaling pathways which may include stimulation of adenylyl cyclase and PLA2.
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PMID:Angiotensin II AT1 receptor/signaling mechanisms in the biphasic effect of the peptide on proximal tubular Na+,K+-ATPase. 960 7

We examined the signal transduction cascade of angiotensin II in isolated rat proximal tubules. Angiotensin II induced a rapid (15 sec) concentration-dependent rise in intracellular free Ca2+ (EC50 = 1.7 nM). The rise in Ca2+ was blocked by the angiotensin II receptor AT1 specific antagonist SK&F 108566. This indicates that the rise in Ca2+ is fully mediated by AT1 receptors. To characterize further the antagonism by SK&F 108566, the Schild analysis was performed (pA2 = 10.9 +/- 0.14 and slope = 0.94 +/- 0.11; n=3). It indicated that SK&F 108566 is a high affinity competitive antagonist at AT1 receptors in the proximal tubule. Angiotensin II signaling also induced a rapid (5 min) rise in cGMP formation. This response was blocked by SK&F 108566, by inhibition of nitric oxide synthase, or by inhibition of soluble guanylyl cyclase. This indicates that the formation of cGMP elicited by angiotensin II is mediated by AT1 receptors and activation of the NO-cGMP pathway. Since cGMP can inhibit Na, K-ATPase activity, activation of the NO-cGMP pathway may act as a negative feedback component of angiotensin II signaling in renal proximal tubules.
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PMID:Angiotensin II signaling activities the NO-cGMP pathway in rat proximal tubules. 969 43

Accumulating evidence suggests that angiotensin-(1-7) is an important component of the renin-angiotensin system, having actions that are either identical to or opposite that of angiotensin II. Angiotensin I can be directly converted to angiotensin-(1-7), bypassing formation of angiotensin II. This pathway is under the control of three enzymes: neutral endopeptidases 24.11 (neprilysin) and 24.15 and prolyl-endopeptidase 24.26. Two of the three angiotensin-forming enzymes (neprilysin and endopeptidase 24.15) also contribute to the breakdown of bradykinin and the atrial natriuretic peptide. Furthermore, angiotensin-(1-7) is a major substrate for angiotensin-converting enzyme. These observations suggest that the process of biotransformation between the various Ang peptides of the renin-angiotensin system and other vasodepressor peptides are intertwined through this enzymatic pathway. Substantial evidence suggests that angiotensin-(1-7) stimulates the synthesis and release of vasodilator prostaglandins, and nitric oxide, while also augmenting the metabolic actions of bradykinin. In addition, angiotensin-(1-7) alters tubular sodium and bicarbonate reabsorption, decreases Na+-K+-ATPase activity, induces diuresis, and exerts a vasodilator effect. These physiologic effects of angiotensin-(1-7) favor a blood pressure-lowering effect. The majority of the data currently available suggest that angiotensin-(1-7) mediates its effects through a novel non-AT1/AT2 receptor subtype.
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PMID:Novel angiotensin peptides regulate blood pressure, endothelial function, and natriuresis. 972 81

-Dopamine and angiotensin II (Ang II) receptors have been reported to exhibit an interaction in renal proximal tubules. The present study was designed to investigate the regulation by a D2-like dopamine receptor of Ang II-mediated stimulation of Na,K-ATPase activity in the renal proximal tubules. Ang II (10(-13) to 10(-9) mol/L) stimulated Na,K-ATPase activity in the proximal tubules that was completely abolished when the tubules were pretreated with the D2-like receptor agonist bromocriptine (1 micromol/L) for 30 minutes. The effect of bromocriptine on Ang II response was prevented by domperidone (1 micromol/L), a D2-like dopamine receptor antagonist. Similarly, the inhibition of forskolin (1 micromol/L)-induced cAMP accumulation caused by Ang II (10 pmol/L) was also abolished in bromocriptine-pretreated tubules. Basal and forskolin-stimulated cAMP was not significantly different in bromocriptine-treated tubules compared with the control. [3H]-Ang II binding sites (angiotensin type 1 [AT1] receptors) were reduced by approximately 65% in bromocriptine-treated proximal tubules, a result that was further substantiated by Western blot analysis revealing a 50% decrease in AT1 receptors in bromocriptine-treated tubules compared with the control. Western blot analysis of G proteins revealed a 2-fold increase in Gsalpha and a 20% decrease in Gialpha1 and Gialpha2 in the bromocriptine-treated proximal tubules. Bromocriptine (1 micromol/L) alone stimulated Na,K-ATPase activity during the first 30 minutes of incubation, and thereafter the stimulation fell to the basal level. Similarly, bromocriptine-mediated inhibition of cAMP lasted only up to 20 minutes. The data suggest that preactivation of D2-like dopamine receptors abolishes Ang II-mediated stimulation of Na,K-ATPase activity and inhibition of cAMP accumulation. This phenomenon may be a consequence of a decrease in AT1 receptors and alterations in G protein levels in the proximal tubules. We propose that such a regulation of Ang II response by bromocriptine is the result of heterologous desensitization of the D2-like receptor system.
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PMID:Bromocriptine regulates angiotensin II response on sodium pump in proximal tubules. 985 73

Angiotensin II (AG II) stimulates the ouabain-insensitive, furosemide- sensitive Na+-ATPase present in the basolateral membrane of pig renal proximal tubules in a dose dependent manner. Maximum effect was obtained with 10-8 M AG II, which corresponded to an activity 134% higher than control. Half of the maximum effect was observed between 10-11 M and 10-10 M, corresponding to physiological hormone levels. Saralasin, an AG II peptide analogue receptor antagonist, abolished the phenomenon, demonstrating that AG II interacts with specific sites in pig proximal tubules. The AG II stimulatory effect was also prevented by dithiothreitol (DTT), a reducing compound, and by 10 nM losartan, a non-peptide antagonist highly specific for AT1 receptors, characterizing AG II binding to AT1 receptors. GTPgammaS, a non-hydrolysable GTP analogue, increased by 159% the enzyme activity as compared to the control values. The simultaneous addition of 10-5 M GTPgammaS and 10-8 M AG II did not have additive effects. Furthermore, the stimulatory action of AG II was completely abolished by 0.1 microM GDPbetaS, a non-hydrolysable GDP analogue. Two microgram ml-1 pertussis toxin, an inhibitor of Gi-protein, did not modulate the AG II stimulatory effect. On the other hand, the Na+-ATPase activity was enhanced 100% in the presence of cholera toxin and 85% in the presence of both AG II and cholera toxin. Taken together, these data suggest that AG II activates the Na+-ATPase activity through AT1 receptors coupled to a pertussis-insensitive and cholera-sensitive G-protein.
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PMID:Angiotensin II activates the ouabain-insensitive Na+-ATPase from renal proximal tubules through a G-protein. 988 88

To evaluate the role of angiotensin II (AII) on diastolic function during post-myocardial infarction (MI) ventricular remodeling, coronary ligation or sham operation was performed in male Sprague-Dawley rats. Experimental animals were maintained on either irbesartan, a selective AT1-receptor antagonist, or no treatment. Measurement of cardiac hypertrophy, diastolic function, and sarcoendoplasmic reticulum adenosine triphosphatase (ATPase; SERCA) and phospholamban (PLB) gene expression was assessed at 6 weeks after MI. Myocardial infarction caused a significant increase in myocardial mass and left ventricular (LV) filling pressure, whereas LV systolic pressure and +dP/dt were reduced. The time constant of isovolumic relaxation (tau) was markedly prolonged after MI. Post-MI hypertrophy was associated with substantial increases in the messenger RNA (mRNA) expression of atrial natriuretic peptide (ANP), but no significant changes in SERCA or PLB levels. Although irbesartan treatment did not significantly alter post-MI LV systolic or filling pressures, it nevertheless effectively decreased ventricular hypertrophy, improved tau, and normalized ANP expression. These results demonstrate that AT1-receptor antagonism has important effects on myocardial hypertrophy and ANP gene expression, which are independent of ventricular loading conditions. In addition, the improvement in diastolic function was not related to changes in SERCA and PLB gene expression, suggesting that enhanced myocardial relaxation was related to the blockade of AII effects on myocyte function or through a reduction of ventricular hypertrophy itself or both.
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PMID:Angiotensin type 1 receptor antagonism with irbesartan inhibits ventricular hypertrophy and improves diastolic function in the remodeling post-myocardial infarction ventricle. 1006 80

In astrocytes the activity of the Na+,K(+)-ATPase pump maintains an inwardly directed electrochemical sodium gradient used by the Na+-dependent transporters and regulates the extracellular K+ concentration essential for neuronal excitability. We show here that incubation of cultured rat astrocytes with angiotensin II (Ang II) modulates Na+,K(+)-ATPase activity, in a dose- and time-dependent manner. Na+,K(+)-ATPase activation was mediated by binding of Ang II to AT1 receptors as it was completely blocked by DuP 753, a specific AT1 receptor subtype antagonist. Stimulation of Na+,K(+)-ATPase activity by Ang II was dependent on protein kinase C (PKC) activation because PKC antagonists abolished the inducing effect of Ang II and the PKC activator phorbol 12-myristate 13-acetate enhanced transporter activity. Ang II stimulated translocation of PKC-delta but not that of other PKC isoforms from the cytosol to the plasma membrane. These results indicate that the activity of Na+,K(+)-ATPase in astrocytes is increased by physiological concentrations of Ang II and that the AT1 receptor subtype mediates the Na+,K(+)-ATPase response to Ang II via PKC-delta activation.
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PMID:Angiotensin II modulates the activity of Na+,K+-ATPase in cultured rat astrocytes via the AT1 receptor and protein kinase C-delta activation. 1069 67


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