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 II (AngII) is a potent regulator of electrolyte transport with biphasic effects on salt and HCO3-resorption in proximal tubule epithelia (PCT). In cultured PCT cells, pM to nM AngII activates a GTP-binding protein to inhibit cAMP formation and thus releases inhibition of apical Na/H exchange. Phospholipase A2 is activated by nM to microM AngII releasing arachidonate which is metabolized by a novel P450 epoxygenase to form 5,6-epoxy-eicosatrienoic acid (5,6-EET). 5,6-EET and nM apical AngII cause dihydropyridine-sensitive Ca2+ influx from the extracellular space, inhibition of apical-to-basolateral Na flux, and decrease in epithelial monolayer short circuit current. 5,6-EET also inhibits Na/K-ATPase by 50%. This P450 epoxygenase is physiologically important in the AngII-signaling system because the P450 inhibitor ketoconazole blocks AngII effects while potentiating exogenous 5,6-EET effects. Finally, these AngII-mediated signaling systems are polarized in the PCT with pM basolateral AngII inhibiting adenylate cyclase and nM apical AngII activating PLA2 and subsequent generation of 5,6-EET.
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PMID:Angiotensin II actions in the rabbit proximal tubule. Angiotensin II mediated signaling mechanisms and electrolyte transport in the rabbit proximal tubule. 170 6

This study examines the receptor mechanisms by which dopamine (DA) inhibits Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity in single permeabilized proximal tubule (PCT). Na(+)-K(+)-ATPase activity was inhibited in the presence of both DA1- and DA2-specific agonists but not by either agonist alone. The inhibition induced by DA (10(-6) M) was attenuated in the presence of either of the two DA2-specific antagonists S-sulpiride and YM 09151 at 10(-5) M and in the presence of the DA1 antagonist SCH 23390 (10(-5) M). PCT adenosine 3',5'-cyclic monophosphate (cAMP) levels were significantly increased in the presence of DA and DA1 agonist, but DA2 agonist had no effect on cell cAMP levels. Na(+)-K(+)-ATPase activity was significantly inhibited in PCT incubated with DA2 agonist (10(-5) M) and dibutyryl (DB)-cAMP (10(-6) M) but not with DA2 agonist (10(-5) M) only. PCT Na(+)-K(+)-ATPase activity was also significantly inhibited in the presence of both DA2 agonist (10(-5) M) and forskolin (10(-6) M). Neither DBcAMP (10(-6) M) nor forskolin (10(-6) M) alone inhibited Na(+)-K(+)-ATPase activity. In tubules incubated with DA (10(-8) to 10(-9) M), the presence of DBcAMP (10(-6) M) enhanced the sensitivity by which DA inhibited Na(+)-K(+)-ATPase activity. We conclude that PCT Na(+)-K(+)-ATPase activity is inhibited by a synergistic action of the DA1 and DA2 receptors, with the DA1 receptor acting to increase cell cAMP levels.
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PMID:Inhibition of proximal tubule Na(+)-K(+)-ATPase activity requires simultaneous activation of DA1 and DA2 receptors. 197 19

The short term regulation of the activity of the Na,K-pump (Na+,K(+)-ATPase) is just beginning to be understood. By using single microdissected proximal tubule segments (PCT) (permeabilized in order to clamp Na entry), it was possible to study regulation of Na+,K(+)-ATPase activity in its own environment and in a well defined cell population. The Na+,K(+)-ATPase activity can be regulated over a short term via guanidine triphosphate (GTP) dependent regulatory proteins. However the guanidine proteins are not directly coupled to the Na,K-pump and the mechanism involves the activation of complex intracellular signalling system. Locally produced dopamine induces a dose dependent inhibition of Na+,K+ ATPase activity. This inhibition is mediated by a complex mechanism that requires the activation of both membrane dopamine receptors, DA-1 and DA-2. It involves the activation of a pertussis toxin sensitive GTP-binding protein and activation of protein kinase C. A DA-2 agonist only inhibits Na+,K(+)-ATPase activity when it is incubated together with dibutyryl cAMP or Forskolin. We have therefore concluded that an increase in cellular cAMP levels plays a permissive role for DA-2 inhibition of Na+,K(+)-ATPase activity. A fully differentiated cell is required for dopamine inhibition of Na+,K(+)-ATPase activity. An abnormal regulation of proximal tubule Na+,K(+)-ATPase activity might be of importance in the pathogenesis of certain types of hypertension.
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PMID:Short-term regulation of Na+,K(+)-ATPase activity by dopamine. 216 34

We have recently demonstrated that dopamine (DA) inhibits Na,K-ATPase in single proximal tubule (PCT) segments dissected from previously collagenase perfused rat kidney. The aim of the present study was to ascertain whether this effect was directly mediated by DA or if DA was the precursor of an inhibitor. When PCT segments were incubated with L-DOPA, Na,K-ATPase was significantly lower than in vehicle incubated tubules. Inhibition of dopa decarboxylase abolished the effect of L-DOPA on Na,K-ATPase activity. The metabolites of DA, 3, 4-dihydroxphenyl acetic acid (DPAC) and homovanillic acid (HVA) both inhibited Na,K-ATPase activity in doses higher than 10(-6) M. Both HVA and DPAC 10(-4) M caused approximately 35% inhibition. Dopamine inhibited Na,K-ATPase activity even in a dose as low as 10(-7) M. Maximal inhibition (greater than 60%) was found with DA-5 M. Na,K-ATPase activity was significantly lower in tubules exposed to DA 10(-4) and 10(-5) M than in tubules exposed to DPAC or HVA 10(-4) and 10(-5) M. Dopamine produced in proximal tubule cells from L-DOPA, is an active inhibitor of the Na,K-pump in these cells. The DA metabolites DPAC and HVA are less potent Na,K-pump-inhibitors.
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PMID:Effect of L-DOPA, dopamine, dihydroxyphenyl acetic acid and homovanillic acid on Na,K-ATPase activity in rat proximal tubule segments. 282 Jan 98

We determined the effect of dexamethasone on Na-K-ATPase activity in six nephron segments of the adrenalectomized rabbit. Treatment consisted of 1.4 micrograms dexamethasone X 100 g body wt-1 X day-1 for 7 days prior to the study of the nephron segments. Enzyme activity was determined in individual nephron segments by a microfluorometric assay. There was 40-50% less activity of Na-K-ATPase in the S1 portion of the proximal convoluted tubule (PCT, S1), the medullary thick ascending limb (MTAL), and the distal convoluted tubule (DCT) of adrenalectomized rabbits compared with that of control (sham-operated) animals. There was no significant difference in the enzyme activity in proximal straight tubules (PST, S2 and S3) and cortical thick ascending limb (CTAL) of adrenalectomized and control animals. Dexamethasone treatment produced a dexamethasone concentration of 5 +/- 0.8 nM in the plasma and increased Na-K-ATPase activity in PCT (S1), MTAL, and DCT of the adrenalectomized animals to the control levels without significantly affecting the enzyme activity in the PST (S2, S3) or CTAL. The concentration of dexamethasone in the plasma was such that the hormone should bind mainly to dexamethasone receptors (Kd = 5 nM) and very little to aldosterone receptors (Kd greater than 60 nM). Thus, glucocorticoids probably stimulate Na-K-ATPase in PCT, MTAL, and DCT through glucocorticoid (Type II) receptors and not through mineralocorticoid (Type I) receptors.
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PMID:Glucocorticoid effects on Na-K-ATPase in rabbit nephron segments. 298 45

Na-K-ATPase activity was studied in tubule segments from the cortex and medulla of rabbit kidneys under normal conditions, after unilateral nephrectomy, and after chronic salt loading. After unilateral nephrectomy kidney weight increased by 37% and Na-K-ATPase activity rose significantly in all nephron segments by 36-200% (P less than 0.01). Oral salt loading for 2 wk with 0.5% NaCl caused an increase in GFR and in absolute sodium excretion as well as reabsorption; plasma aldosterone decreased by 44% (P less than 0.005). In the proximal segments (PCT, CPST, OMPST, and TDL) there were no marked changes in Na-K-ATPase activity, whereas along the whole length of the ascending limb of Henle's loop (iMTAL, MTAL, and CTAL) there was a significant rise in the enzymatic activity of 30-200% (P less than 0.02). In the distal segments (DCT, CCD, and OMCD) there was a marked decrease of 50-60% (P less than 0.005) in Na-K-ATPase activity after the salt loading. We conclude that unilateral nephrectomy caused a general increase in Na-K-ATPase activity along the whole length of the nephron, and salt loading caused a selective increase in enzyme activity along the ascending limb of Henle's loop and decrease in the distal segments.
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PMID:Na-K-ATPase in isolated rabbit tubules after unilateral nephrectomy and Na+ loading. 298 46

Dopamine (DA) produces a natriuresis attributed in part to inhibition of Na,K-ATPase activity (NKA) in the proximal tubule (PCT), and impairment in this inhibition has been linked to several forms of hypertension in animals. Here we examined whether the intracellular signaling mechanisms involved are the same in the early and late phases of this phenomenon. DA (1 microM) inhibited NKA similarly after 15 min (by 38%) or 180 min (by 36%) incubation, taken to represent short-term (ST) and sustained (Sd) pump regulation, respectively. Calphostin C, a specific inhibitor of protein kinase C (PKC), completely blocked the ST action of DA on NKA, whereas IP20, a specific inhibitor of protein kinase (PKA), had no effect. In contrast, IP20 completely abolished the Sd (180 min) inhibition by DA, whereas calphostin C had only a partial or variable effect. The DA-1 agonist fenoldopam (which does not activate PKC but increases cAMP) alone failed to inhibit the pump at 180 min (as it does also in the short-term in PCT), suggesting that ST inhibition is required for the Sd effect to occur. Furthermore, PTH1-34, a known ST inhibitor of NKA suppressed the pump at 180 min (by 46%), but unlike in the short-term, this effect was completely prevented by IP20. In contrast, PTH3-34, which does not stimulate adenylyl cyclase or activate PKA, caused only a small (19%) and variable Sd inhibition. In conclusion, short-term inhibition of the PCT pump by dopamine is mediated via PKC, whereas the sustained inhibition requires the PKA pathway in addition to the ongoing PKC-mediated effect.
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PMID:Short-term vs. sustained inhibition of proximal tubule Na,K-ATPase activity by dopamine: cellular mechanisms. 902 36

The enzyme catechol-O-methyltransferase (COMT), which plays an important role for dopamine metabolism, is abundantly expressed in the kidney. To test whether the natriuretic effects of dopamine may be related to the rate of dopamine metabolism, rats were treated with nitecapone, a peripheral inhibitor of COMT. Nitecapone, given by gavage, induced a highly significant (5.6-fold) increase in sodium excretion, which was associated with an inhibition of the Na+,K+-ATPase activity in both the proximal convoluted and proximal straight tubules (PCT and PST, respectively). These effects were completely abolished if the rats were also treated with a specific dopamine 1 antagonist, SCH 23390. Furthermore, the natriuretic effect of nitecapone was also observed in rats on a high salt diet. The kidney-specific pro-drug to dopamine, glu-dopa, induced a significant, but less pronounced increase in urinary sodium excretion, associated with a dopamine-dependent inhibition of the Na+,K+-ATPase activity in the PCT but not in the PST. Nitecapone and glu-dopa had an additive natriuretic effect. It is concluded that COMT plays an important role in determining the natriuretic effects of the renal dopamine system.
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PMID:Inhibition of COMT induces dopamine-dependent natriuresis and inhibition of proximal tubular Na+,K+-ATPase. 929 Nov 95

The compensatory hypertrophy in different renal cortical structures was studied in rats 10 and 21 days after unilateral nephrectomy (UNX). Quantitative morphological/stereological analysis revealed significant increases in total renal cortical volume--33% on day 10 and 48% on day 21--after UNX. These changes were paralleled by significant increments in the volumes of proximal convoluted tubule (PCT, 55%), distal convoluted tubule (DCT, 114%), and cortical collecting duct (CCD, 106%) segments on day 10. The corresponding changes on day 21 were 76, 122, and 212%, respectively. These alterations were accompanied by increases in segment length; 3% PCT, 23% DCT, and 50% CCD on day 10 and 9% PCT, 30% DCT, and 142% CCD on day 21 after UNX. The total luminal and basolateral cell membrane surface areas also exhibited a time-dependent increase after UNX. The increments in both luminal and basolateral membrane domains in PCT and DCT after 10 days were not significant, but reached significance after 21 days (PCT: luminal membrane 21%, basolateral membrane 63%; DCT: luminal membrane 98%, basolateral membrane 63%). In contrast, CCD membrane areas had increased substantially already 10 days after UNX (luminal membrane 92%, basolateral membrane 71%). It declined subsequently by day 21 (luminal membrane 57%, basolateral membrane 32%). The cell rubidium concentration after a 30-second rubidium infusion, an index of Na-K-ATPase activity, as well as sodium concentrations were unaltered in cells of all nephron segments investigated. Altogether the stereological analysis shows that the compensatory increase in organ volume can be attributed primarily to an increase in nephron epithelial volume. The PCT responds with 'radial' hypertrophy (thickening of the tubular epithelial wall), while the DCT undergoes 'length' hypertrophy (increase of tubular length without thickening of the tubular wall and without an increase in number of cells). This type of hypertrophy is especially prominent on day 21 after UNX for the CCD which doubles in length. Only on day 10 does the CCD seem to respond with hyperplasia. Adaptive changes in response to UNX develop gradually. Only a few of the morphological parameters studied had completed their change by 10 days, the majority required longer.
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PMID:Quantitative morphology of renal cortical structures during compensatory hypertrophy. 969 94

The cellular site of erythropoietin (epo) production within the mammalian kidney is still not completely understood. In the present study, we examined the expression of epo mRNA in microdissected rat nephron segments by RT-PCR after induction of epo expression with cobalt chloride. Erythropoietin mRNA was not detected in nephron segments from saline injected rats. In cobalt chloride injected animals, epo mRNA was found in the majority of samples from the cortical region of the nephron, PCT, and CAL. Medullary tubule preparations (MCT and MAL) were mostly negative for epo mRNA, and glomeruli were uniformly negative. The induction of epo transcripts in tubular cells by cobalt chloride was paralleled by stimulation of the major transport enzyme in the kidney, namely, Na-K ATPase in a tubular profile similar to that of induction of epo transcripts. These results support some earlier findings that epo gene expression in response to cobalt salt stimulation of rat kidney occurs in transporting tubular epithelial cells.
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PMID:Erythropoietin is produced by tubular cells of the rat kidney. 1009 26


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