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)

Dopamine's modulatory actions on signal transduction in the spontaneously hypertensive rat (SHR) proximal tubule are blunted; therefore, it was predicted that dopamine does not regulate phosphate (Pi) reabsorption in SHR. To test this hypothesis, dopamine production was inhibited with carbidopa (10 mg/kg ip) 18 h before and during clearance measurements of chronically denervated SHR and Wistar-Kyoto (WKY) rat kidneys. Dopamine excretion decreased 80% from SHR and 85% from WKY rats. Pi excretion decreased 60 to 67%. Plasma Pi and calcium, inulin clearance, and Na excretion did not change. Citrate excretion, which reflects proton secretion by proximal tubules, decreased 72% from WKY rats. Citrate excretion was significantly lower from SHR (5 +/- 10 pmol/min) than from WKY rats (73 +/- 11 pmol/min) and was not altered by carbidopa. Carbidopa, injected 18 and 1 h before kidneys were collected, increased NaK-ATPase in cortical basolateral membranes from WKY rats (27%) but not in membranes from SHR. After the incubation of renal cortical minceates for 15 min with L-DOPA (10(-5) M), there was no change in brush border membrane vesicle uptake of 32Pi, (3H)glucose, or (14C)citrate. Incubation with carbidopa (10(-4) M) increased 32Pi uptake by 11% (P < 0.001) and (3H)glucose uptake by 9% (P = 0.02). (14C)citrate uptake was not increased by carbidopa but was higher in SHR (977 +/- 2 pmol/10 s.mg) than in WKY rats (823 +/- 43 pmol/10 s.mg; P = 0.04). In summary, dopamine produced in WKY rat and SHR proximal tubules decreases Pi uptake by using a signaling process distinct from those that regulate NaK-ATPase and the antiporter.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous dopamine regulates phosphate reabsorption but not NaK-ATPase in spontaneously hypertensive rat kidneys. 784 53

Dopamine is one of the major natriuretic hormone. It acts as an autocrine or paracrine factor to inhibit Na+ transport in several tubular segments. Na+,K(+)-ATPase is an important target protein for dopamine. Studies of the tubular effects of dopamine have provided new information about the coupling of dopamine to intracellular signaling systems and about the molecular mechanism for dopamine interaction with other hormones. Several lines of evidence now suggest that abnormalities of the renal dopamine system can lead to salt-sensitive hypertension.
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PMID:Dopamine action and metabolism in the kidney. 785 Apr 10

Dopamine has an age-dependent natriuretic and diuretic effect. We have investigated the ontogeny of the dopamine response on adenylate cyclase activity and Na+,K(+)-ATPase activity in two different cell populations in the infant (10-d-old) and the adult (40-d-old) rat kidney. Basal- and forskolin-stimulated adenylate cyclase activity in tubular suspensions of renal cortex was 5.4-fold (p < 0.05) higher in the 10-d-old rats than in the 40-d-old rats but unchanged between the ages in a suspension of medullary tubules. The dopamine-1-specific agonist fenoldopam did not stimulate adenylate cyclase activity in the cortical cells from 10-d-old rats but did stimulate activity 51 +/- 16% (p < 0.05) in the 40-d-old rats. In the medullary suspension, fenoldopam stimulated adenylate cyclase activity by 43.5 +/- 5% (p < 0.001) in the 10-d-old rats and by 32.0 +/- 7% (p < 0.01) in the 40-d-old rats. In the isolated proximal convoluted tubule, dopamine inhibited Na+,K(+)-ATPase activity in both the 10-d-old (34 +/- 3%, p < 0.001) and 40-d-old rats (44 +/- 7%, p < 0.001). In contrast, in the medullary thick ascending limb of Henle, inhibition of Na+,K(+)-ATPase activity by fenoldopam was more pronounced in the 10-d-old (56 +/- 6%, p < 0.001) than in the 40-d-old rat (33 +/- 6%, p < 0.001). In summary, the renal tubular effects of dopamine on adenylate cyclase and Na+,K(+)-ATPase activity change during postnatal development in a cell-specific manner.
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PMID:The effect of dopamine on adenylate cyclase and Na+,K(+)-ATPase activity in the developing rat renal cortical and medullary tubule cells. 790 83

We examined the effect of endogenous dopamine production on Pi and citrate excretion by Wistar rats. Carbidopa (20-40 mumol/kg ip) decreased dopamine, Pi, and citrate excretion within 20 min (86%, 47%, and 38%, respectively); Pi reabsorption increased 11 +/- 4% (P = 0.03). The decreases were sustained for at least 18 h. 3-Hydroxybenzylhydrazine (45 mumol/kg ip) reduced Pi excretion 24%. Benserazide (40 mumol/kg ip and 0.1 mumol/min iv) reduced dopamine excretion (94%) and blocked the effect of carbidopa on Pi and citrate excretion. In isolated perfused kidneys benserazide, carbidopa, and 3-hydroxybenzylhydrazine all decreased Pi excretion. Dopamine (1 mumol/l) added to cortical minceates reduced brush-border membrane vesicle (BBMV) 32P uptake by 8% (P < 0.02) and amiloride-inhibitable 22Na uptake by 19%. Carbidopa added to minceates increased 32P uptake by 12%. Carbidopa pretreatment increased (75%) amiloride-sensitive 22Na uptake into BBMV of rats fed a high-salt diet. Uptake was not increased into BBMV from rats fed a low-salt diet. Carbidopa increased (17%) basolateral membrane Na(+)-K(+)-adenosinetriphosphatase (Na(+)-K(+)-ATPase) gradually over 4 h. Na(+)-K(+)-ATPase did not increase in rats fed a low-phosphorous diet, but did increase when dopa was added to the diet. Thus endogenous dopamine appears to directly control Na(+)-Pi and Na+/H+ transport and secondarily alter basolateral membrane Na(+)-K(+)-ATPase.
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PMID:Endogenous renal dopamine production regulates phosphate excretion. 802 66

Endogenous kidney dopamine (DA) causes natriuresis and diuresis, at least partly, via inhibition of proximal tubular Na+,K(+)-ATPase. The present study was done to identify the dopamine receptor subtype(s) involved in dopamine-induced inhibition of Na+,K(+)-ATPase activity. Suspensions of renal proximal tubules from Sprague-Dawley rats were incubated with dopamine, the DA-1 receptor agonist fenoldopam or the DA-2 receptor agonist SK&F 89124 in the presence or absence of either the DA-1 receptor antagonist SCH 23390 or the DA-2 receptor antagonist domperidone. Dopamine and fenoldopam (10(-5) to 10(-8) mol/l) produced a concentration-dependent inhibition of Na+,K(+)-ATPase activity. However, SK&F 89124 failed to produce any significant effect over the same concentration range. Incubation with fenoldopam (10(-5) to 10(-8) mol/l) in the presence of SK&F 89124 (10(-6) mol/l) inhibited Na+,K(+)-ATPase activity to a degree similar to that with fenoldopam alone. Furthermore, DA-induced inhibition of Na+,K(+)-ATPase activity was attenuated by SCH 23390, but not by domperidone. Since alpha-adrenoceptor activation is reported to stimulate Na+,K(+)-ATPase activity and, at higher concentrations, dopamine also acts as an alpha-adrenoceptor agonist, the potential opposing effect from alpha-adrenoceptor activation on DA-induced inhibition of Na+,K(+)-ATPase activity was investigated by using the alpha-adrenoceptor blocker phentolamine. We found that, in the lower concentration range (10(-5) to 10(-7) mol/l), dopamine-induced inhibition of Na+,K(+)-ATPase activity in the presence of phentolamine was similar in magnitude to that observed with dopamine alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of Na+,K(+)-ATPase in rat renal proximal tubules by dopamine involved DA-1 receptor activation. 809 67

Dopamine is a natriuretic hormone that acts by inhibiting tubular Na+, K(+)-ATPase activity by activation of the dopamine-1 receptor (the thick ascending limb [TAL] of Henle) or by a synergistic effect of dopamine-1 and dopamine-2 receptors (the proximal tubule). The dopamine-1 receptor is coupled to adenylate cyclase. In this article we show that prehypertensive Dahl salt-sensitive (DS) rats have a blunted natriuretic response to dopamine determined during euvolemic conditions compared with Dahl salt-resistant (DR) rats. Furthermore, we have examined the renal tubular effects of dopamine in DS and DR rats. Basal Na+,K(+)-ATPase activity was similar in DS and DR rats. In proximal tubule, dopamine (10(-5) M) inhibited Na+,K(+)-ATPase activity in DR but not in DS rats. The dopamine-2 agonist LY171555 (10(-5) M) together with dibutyryl cyclic AMP (10(-6) M) inhibited proximal tubule Na+,K(+)-ATPase activity in both DS and DR rats. LY171555 alone had no effect. In TAL, the dopamine-1 agonist fenoldopam (10(-5) M) inhibited Na+,K(+)-ATPase activity in DR but not in DS rats. Dibutyryl cyclic AMP (10(-5) M) inhibited TAL Na+,K(+)-ATPase activity in both DS and DR rats. In cell suspensions from the cortex and the medulla, activation of the dopamine-1 receptor significantly increased cyclic AMP content in DR but not in DS rats. The results indicate that DS rats lack the capacity to inhibit tubular Na+,K(+)-ATPase activity because of a defective dopamine-1 receptor adenylate cyclase coupling. This defect may contribute to the impaired natriuretic capacity in DS rats.
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PMID:Dopamine regulation of renal Na+,K(+)-ATPase activity is lacking in Dahl salt-sensitive rats. 809 63

1. The temporal relationship between the excretion of dopamine and sodium transport inhibitor (STI) during salt loading was examined in the rat. 2. Urine samples were collected before and during salt loading (given as 18 g/l NaCl solution to replace drinking water) for the measurement of sodium, creatinine, dopamine and STI in 6 female rats. Dopamine was measured by HPLC and STI was extracted and measured by its ability to inhibit purified Na+, K(+)-ATPase enzyme. 3. Urinary sodium and STI (expressed in relation to creatinine) on day 1 of salt loading were 4.6 and 4.2 times respectively of the control values. Urinary excretion of dopamine did not increase significantly until day 2 when it was 21% higher. 4. The excretion of STI paralleled that of sodium excretion whereas the excretion of dopamine lagged behind. 5. We conclude that salt loading increases STI and dopamine and that the increase in STI precedes that of dopamine.
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PMID:The effect of salt loading on the urinary excretion of dopamine and sodium transport inhibitor in the rat. 819 6

DARPP-32 is a dopamine- and cAMP-regulated inhibitor of protein phosphatase-1 (PP-1). Dopamine and DARPP-32 regulate sodium reabsorption in renal tubules by inhibiting the activity of Na+,K(+)-ATPase. We here report the pre- and postnatal distributions of DARPP-32 in the kidney as demonstrated by immunoblotting and immunohistochemistry. With immunoblotting we examined the abundance of DARPP-32 and the functionally similar but more widespread inhibitor of PP-1, inhibitor-1 (I-1). We compared their relative abundance in the renal cortex, renal medulla and neostriatum from the brain, where DARPP-32 is greatly enriched. DARPP-32 levels in the adult rat were fourfold higher in the neostriatum than in the renal medulla and 13-fold higher than in the renal cortex. I-1 levels were approximately the same in the neostriatum and in the renal medulla and 2.5-fold higher in neostriatum than in the renal cortex. Between postnatal day 10 (PN10) and 40 (PN40) DARPP-32 abundance increased 1.3-fold in the neostriatum, 1.4-fold in the renal cortex and sixfold in the medulla. The abundance of I-1 did not increase in the striatum from PN10 to PN40 but increased 1.5-fold in the renal cortex and threefold in the renal medulla. Thus, during the time of maturation of tubular transport function, the levels of both PP-1 inhibitors increased in the kidney, the largest increase being found in the renal medulla. With immunohistochemistry strong DARPP-32-like-immunoreactivity (DARPP-32-LI) was detected in the ureteral buds from gestational day 18 and up to postnatal day 8 when nephrogenesis was completed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distribution of dopamine- and cAMP-dependent phosphoprotein (DARPP-32) in the developing and mature kidney. 823 Oct 21

Some polychlorinated biphenyls (PCBs) have been reported to alter locomotor activity and decrease brain dopamine function in laboratory animals. PCBs with ortho- and/or parachlorine substitutions and varying number of chlorinations are known to decrease cell dopamine content in vitro and have been detected in brains of animals exposed to PCBs, suggesting that the neurotoxicity could be mediated by ortho-substituted congeners. Dopamine or other neurotransmitter uptake and release phenomena are dependent on the maintenance of intracellular Ca2+ homeostasis, and perturbations in Ca2+ homeostasis could lead to altered cell function and/or death. We compared the effects of two PCB congeners on Ca2+ homeostasis in cerebellar granule cells: 2,2'-dichlorobiphenyl (DCBP), a putative neurotoxic congener, and 3,3',4,4',5-pentachlorobiphenyl (PCBP), a presumed nonneurotoxic congener. In cerebellar granule cells (6-8 days in vitro), DCBP was cytotoxic as indicated by a significant increase in LDH leakage at 200 microM after 2 hr of exposure and at 100 microM after 4 hr exposure. PCBP, on the other hand, did not affect LDH leakage even at 200 microM for up to 4 hr. Although both congeners increased cerebellar granule cell [Ca2+]i, DCPB was more effective in increasing [Ca2+]i to a greater extent than PCBP. The increase in [Ca2+]i produced by both congeners was not transient, but a steady rise was observed with time. To understand cellular Ca(2+)-buffering capacity, Ca2+ sequestration and Ca2+ extrusion were studied in mitochondria, microsomes, and synaptosomes, isolated from adult rat cerebellum. DCBP was a potent inhibitor of 45Ca2+ uptake by mitochondria (IC50 = 6.17 +/- 0.53 microM) and microsomes (IC50 = 7.61 +/- 0.35 microM). PCBP inhibited Ca2+ sequestration by mitochondria (68% of control) and microsomes (72% of control), but the effects were much less than those produced by equivalent concentrations of DCBP. Synaptosomal Ca(2+)-ATPase was inhibited by DCBP, but not by PCBP. These results indicate that at concentrations where cytotoxicity in cerebellar granule cells was not observed, DCBP increased intracellular [Ca2+]i, and at the same concentrations, Ca2+ sequestration by intracellular organelles and Ca(2+)-ATPase in synaptic plasma membrane were inhibited. Although PCBP increased [Ca2+]i in cerebellar granule cells to some extent, it was not potent in affecting Ca2+ sequestration or Ca2+ extrusion in adult cerebellar components. Hence, PCBP-induced slight increase of [Ca2+]i levels in the cells might have been associated with effective Ca2+ sequestration by intracellular organelles, as seen in cerebellar preparations. The results of this study support the hypothesis that the position of chlorine substitution on the biphenyl ring and/or number of chlorine substitutions may have significant implications for predicting potential effects of PCB congeners in the nervous system, and perturbations in Ca2+ homeostasis might play a significant role in the neuroactivity of PCBs.
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PMID:Comparative effects of two polychlorinated biphenyl congeners on calcium homeostasis in rat cerebellar granule cells. 823 68

The catecholamines dopamine and norepinephrine, play a central role in the regulation of sodium homeostasis and blood pressure. Dopamine inhibits tubular Na+, K(+)-ATPase activity and increases sodium excretion. Norepinephrine stimulates Na+, K(+)-ATPase activity and decreases urinary sodium excretion. The signaling pathway by which these two opposite first messengers regulate Na+, K(+)-ATPase activity involves the dopamine-specific protein phosphatase-1 inhibitor, DARPP-32, and the norepinephrine-activated protein phosphatase-2B, calcineurin. Aberrations in the renal dopamine/norepinephrine system may be the cause of alterations in the regulation of sodium excretion during ontogeny and in salt-sensitive hypertension.
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PMID:Molecular mechanisms involved in catecholamine regulation of sodium transport. 838 80


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