Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In rat outer medullary collecting duct (OMCD), the mechanism(s) and regulation of H+ secretion are not understood fully. The effect of changes in acid-base balance and the renin-angiotensin system on net H+ secretion was explored. Rats received NaCl, NaHCO3, NH4Cl, or nothing in their drinking water for 7 days. Total ammonia and total CO2 (JtCO2) fluxes were measured in OMCD tubules perfused in vitro from rats in each treatment group. JtCO2 was reduced in tubules from rats drinking NH4Cl relative to those drinking NaHCO3. Because NH4Cl intake increases plasma renin and aldosterone, we asked if upregulation of the renin-angiotensin system reduces net H+ secretion. Deoxycorticosterone pivalate administered in vivo did not affect JtCO2. However, ANG II given in vivo at 0.1 ng/min reduced JtCO2 by 35%. To determine if ANG II has a direct effect on acid secretion, JtCO2 was measured with ANG II applied in vitro. ANG II (10-8 M) present in the bath solution reduced JtCO2 by 35%. This ANG II effect was not observed in the presence of the AT1 receptor blocker candesartan. In conclusion, in rat OMCD, JtCO2 is paradoxically reduced with NH4Cl ingestion. Increased circulating ANG II, as occurs during metabolic acidosis, reduces JtCO2.
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PMID:ANG II reduces net acid secretion in rat outer medullary collecting duct. 1285 Dec 54

Along the collecting duct, secretion of ammonium (NH) is thought to occur through active H+ secretion in parallel with the non-ionic diffusion of ammonia (NH3). Thus NH3 is secreted into the collecting duct lumen down its concentration gradient. Moreover, the low NH permeability and high NH3 permeability observed in collecting duct epithelia minimizes back diffusion of NH. In general, an increase in the NH3 concentration gradient between the interstitium and the collecting duct lumen correlates with increased NH secretion. However, our laboratory and others have shown an important role of direct NH transport by the Na,K-ATPase. As K+ and NH compete for a common extracellular binding site on the Na,K-ATPase, reduced interstitial K+ concentration, such as during hypokalemia, augments NH uptake. Na,K-ATPase-mediated NH uptake provides an important source of H+ for net acid secretion during hypokalemia and contributes to the increase in NH excretion and metabolic alkalosis observed in this treatment model.
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PMID:Mechanisms of NH4+ and NH3 transport during hypokalemia. 1465 69

A family of ammonium transporter proteins was recently identified. Members of this family, Rh B Glycoprotein (RhBG) and Rh C Glycoprotein (RhCG) are expressed in the kidney and the liver, important tissues for ammonium metabolism. Immunohistochemical studies demonstrate basolateral RhBG immunoreactivity in the connecting segment (CNT) and collecting ducts, but not in the proximal tubule or the loop of Henle. Colocalization with thiazide sensitive cotransporter and carbonic anhydrase II confirms expression in the CNT, initial collecting tubule (ICT), and throughout the collecting duct. Colocalization with AE1 and pendrin demonstrates expression is greatest in A-type intercalated cells in the cortical collecting duct (CCD), outer medullary collecting duct (OMCD) and inner medullary collecting duct (IMCD), present in the CCD principal cell, and not detectable in either pendrin-positive CCD intercalated cells or in non-intercalated cells in the OMCD and IMCD. RhCG immunoreactivity has a similar axial distribution as RhBG. However, RhCG immunoreactivity is apical, and is detectable in all CCD and outer stripe of OMCD cells. The liver, a second organ involved in ammonia metabolism, also expresses both RhBG and RhCG. Basolateral RhBG immunoreactivity is present in the perivenous hepatocyte, but is not present in either the periportal or mid-zonal hepatocyte. Hepatic RhCG mRNA is expressed at lower levels than RhBG, and RhCG protein is detected in bile duct epithelium. These findings indicate that RhBG and RhCG are involved in at least two organs that transport ammonia, and that they are located in sites where they are likely to mediate important roles in ammonia transport.
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PMID:Renal and hepatic expression of the ammonium transporter proteins, Rh B Glycoprotein and Rh C Glycoprotein. 1465 70

The renal collecting duct is the primary site for the ammonia secretion necessary for acid-base homeostasis. Recent studies have identified the presence of putative ammonia transporters in the collecting duct, but whether the collecting duct has transporter-mediated ammonia transport is unknown. The purpose of this study was to examine basolateral ammonia transport in the mouse collecting duct cell (mIMCD-3). To examine mIMCD-3 basolateral ammonia transport, we used cells grown to confluence on permeable support membranes and quantified basolateral uptake of the radiolabeled ammonia analog [14C]methylammonia ([14C]MA). mIMCD-3 cell basolateral MA transport exhibited both diffusive and transporter-mediated components. Transporter-mediated uptake exhibited a Km for MA of 4.6 +/- 0.2 mM, exceeded diffusive uptake at MA concentrations below 7.0 +/- 1.8 mM, and was competitively inhibited by ammonia with a Ki of 2.1 +/- 0.6 mM. Transporter-mediated uptake was not altered by inhibitors of Na+-K+-ATPase, Na+-K+-2Cl(-) cotransporter, K+ channels or KCC proteins, by excess potassium, by extracellular sodium or potassium removal or by varying membrane potential, suggesting the presence of a novel, electroneutral ammonia-MA transport mechanism. Increasing the outwardly directed transmembrane H+ gradient increased transport activity by increasing Vmax. Finally, mIMCD-3 cells express mRNA and protein for the putative ammonia transporter Rh B-glycoprotein (RhBG), and they exhibit basolateral RhBG immunoreactivity. We conclude that mIMCD-3 cells express a basolateral electroneutral NH4+/H+ exchange activity that may be mediated by RhBG.
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PMID:Basolateral ammonium transport by the mouse inner medullary collecting duct cell (mIMCD-3). 1514 71

The collecting duct is the primary site of urinary ammonia secretion; the current study determines whether apical ammonia transport in the mouse inner medullary collecting duct cell (mIMCD-3) occurs via nonionic diffusion or a transporter-mediated process and, if the latter, presents the characteristics of this apical ammonia transport. We used confluent cells on permeable support membranes and examined apical uptake of the ammonia analog [(14)C]methylammonia ([(14)C]MA). mIMCD-3 cells exhibited both diffusive and saturable, transporter-mediated, nondiffusive apical [(14)C]MA transport. Transporter-mediated [(14)C]MA uptake had a K(m) of 7.0 +/- 1.5 mM and was competitively inhibited by ammonia with a K(i) of 4.3 +/- 2.0 mM. Transport activity was stimulated by both intracellular acidification and extracellular alkalinization, and it was unaltered by changes in membrane voltage, thereby functionally identifying an apical, electroneutral NH(4)(+)/H(+) exchange activity. Transport was bidirectional, consistent with a role in ammonia secretion. In addition, transport was not altered by Na(+) or K(+) removal, not inhibited by luminal K(+), and not mediated by apical H(+)-K(+)-ATPase, Na(+)-K(+)-ATPase, or Na(+)/H(+) exchange. Finally, mIMCD-3 cells express the recently identified ammonia transporter family member Rh C glycoprotein (RhCG) at its apical membrane. These studies indicate that the renal collecting duct cell mIMCD-3 has a novel apical, electroneutral Na(+)- and K(+)-independent NH(4)(+)/H(+) exchange activity, possibly mediated by RhCG, that is likely to mediate important components of collecting duct ammonia secretion.
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PMID:Apical ammonia transport by the mouse inner medullary collecting duct cell (mIMCD-3). 1579 90

The erythrocyte Rh-associated glycoprotein (RhAG) was recently found to mediate transport of ammonia/ammonium when expressed in Xenopus laevis oocytes and yeast Saccharomyces cerevisiae. Nonerythroid homologs, RhBG and RhCG, are expressed in the mammalian kidney connecting segment and the collecting duct, major sites of urinary ammonia secretion. This study characterizes the transport properties of murine RhBG and RhCG by ammonium analog [14C]methylamine (MA) uptake and two-electrode voltage clamping of X. laevis oocytes. Both RhBG and RhCG mediated transport of ammonia, but differed in affinity for substrate (K(m) = 2.5 and 10 mM, respectively). The rates of RhBG- and RhCG-mediated transport were sensitive to the concentration of the protonated MA species and were stimulated by extracellular alkalosis and inhibited by acidosis, suggesting a role for H+ in the transport process. Whereas expression of RhBG or RhCG caused a small increase in plasma membrane conductance, [14C]MA uptake was not affected by depolarization of oocytes with 100 mM extracellular K+ or by clamping the membrane potential between 0 and -100 mV, indicating that RhBG- and RhCG-mediated transport was independent of the membrane potential. These results strongly suggest that RhBG and RhCG transport ammonia by an electroneutral process that involves NH4(+)/H+ exchange resulting in net NH3 translocation. The polarized localization of RhBG and RhCG in kidney tubules and the different substrate affinities may enable these proteins to participate in transepithelial ammonia secretion and to therefore play an important role in whole animal acid-base regulation.
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PMID:Characterization of ammonia transport by the kidney Rh glycoproteins RhBG and RhCG. 1613 48

Chronic metabolic acidosis induces dramatic increases in net acid excretion that are predominantly due to increases in urinary ammonia excretion. The current study examines whether this increase is associated with changes in the expression of the renal ammonia transporter family members, Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg). Chronic metabolic acidosis was induced in Sprague-Dawley rats by HCl ingestion for 1 wk; control animals were pair-fed. After 1 wk, metabolic acidosis had developed, and urinary ammonia excretion increased significantly. Rhcg protein expression was increased in both the outer medulla and the base of the inner medulla. Intercalated cells in the outer medullary collecting duct (OMCD) and in the inner medullary collecting duct (IMCD) in acid-loaded animals protruded into the tubule lumen and had a sharp, discrete band of apical Rhcg immunoreactivity, compared with a flatter cell profile and a broad band of apical immunolabel in control kidneys. In addition, basolateral Rhcg immunoreactivity was observed in both control and acidotic kidneys. Cortical Rhcg protein expression and immunoreactivity were not detectably altered. Rhcg mRNA expression was not significantly altered in the cortex, outer medulla, or inner medulla by chronic metabolic acidosis. Rhbg protein and mRNA expression were unchanged in the cortex, outer and inner medulla, and no changes in Rhbg immunolabel were evident in these regions. We conclude that chronic metabolic acidosis increases Rhcg protein expression in intercalated cells in the OMCD and in the IMCD, where it is likely to mediate an important role in the increased urinary ammonia excretion.
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PMID:Renal expression of the ammonia transporters, Rhbg and Rhcg, in response to chronic metabolic acidosis. 1614 66

The primary mechanism by which the kidneys mediate net acid excretion is through ammonia metabolism. In the current study, we examined whether chronic metabolic acidosis, which increases ammonia metabolism, alters the cell-specific and/or the subcellular expression of the ammonia transporter family member, Rhcg, in the outer medullary collecting duct in the inner stripe (OMCDi). Chronic metabolic acidosis was induced in normal SD rats by HCl ingestion for 7 days; controls were pair-fed. The subcellular distribution of Rhcg was determined using immunogold electron microscopy and morphometric analyses. In intercalated cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane. Intracellular Rhcg decreased significantly, and basolateral Rhcg was unchanged. Because apical plasma membrane length increased in parallel with apical Rhcg immunolabel, apical plasma membrane Rhcg density was unchanged. In principal cells, acidosis increased total Rhcg, apical plasma membrane Rhcg, and the proportion of total cellular Rhcg in the apical plasma membrane while decreasing the intracellular proportion. In contrast to the intercalated cell, chronic metabolic acidosis did not significantly alter apical boundary length; accordingly, apical plasma membrane Rhcg density increased. In addition, basolateral Rhcg immunolabel increased in response to chronic metabolic acidosis. These results indicate that in the rat OMCDi 1) chronic metabolic acidosis increases apical plasma membrane Rhcg in both the intercalated cell and principal cell where it may contribute to enhanced apical ammonia secretion; 2) increased apical plasma membrane Rhcg results from both increased total protein and changes in the subcellular distribution of Rhcg; 3) the mechanism of Rhcg subcellular redistribution differs in intercalated and principal cells; and 4) Rhcg may contribute to regulated basolateral ammonia transport in the principal cell.
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PMID:Changes in subcellular distribution of the ammonia transporter, Rhcg, in response to chronic metabolic acidosis. 1643 69

A novel family of proteins, the Mep/AMT/Rh glycoprotein family may mediate important roles in transmembrane ammonia transport in a wide variety of single-celled and multicellular organisms. Results from our laboratory have examined the expression of the non-erythroid proteins, Rh B Glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg), in a wide variety of mammalian tissues. In the kidney, Rhbg and Rhcg are present in distal nephron sites responsible for ammonia secretion. In the mouse kidney, Rhbg immunoreactivity is exclusively basolateral and Rhcg immunoreactivity is exclusively apical, whereas in the rat kidney Rhcg exhibits both apical and basolateral expression. Chronic metabolic acidosis increases Rhcg expression in the outer and inner medulla of the rat kidney; these changes, at least in the outer medullary collecting duct, involve changes in total cellular protein expression in both principal and intercalated cell and changes in its subcellular localization. In the liver, Rhbg is present in the basolateral plasma membrane of the perivenous hepatocyte and Rhcg is present in bile duct epithelia. In the gastrointestinal tract, Rhbg and Rhcg exhibit cell-specific, axially heterogeneous, and polarized expression. These patterns of expression are consistent with Rhbg and Rhcg mediating important roles in mammalian ammonia biology. The lack of the effect of chronic metabolic acidosis on Rhbg expression raises the possibility that Rhbg may function either as ammonia sensing-protein or that it may mediate roles other than ammonia transport.
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PMID:Expression of the non-erythroid Rh glycoproteins in mammalian tissues. 1656 23

The recently cloned, non-erythrocyte Rh glycoproteins (Rhbg and Rhcg) are expressed in the intercalated cells of the renal collecting duct. The apical Rhcg and the basolateral Rhbg are likely involved in NH3 and/or NH4+ transport, yet the characteristics of this transport are not yet certain. In this study we investigated the mechanism of NH4+ transport by Rhbg and Rhcg expressed in Xenopus oocytes. We used a two-electrode voltage-clamp and ion-selective microelectrodes to measure NH4+-induced currents (I(NH4)) and changes in pHi, respectively. In oocytes expressing Rhcg, exposure to bath [NH4+] of 2.5-20 mM induced inward currents that were slightly more than those in H2O-injected (control) oocytes. I-V plots in the presence of NH4+ showed a small increase in slope conductance only at positive potentials. On the other hand, in oocytes expressing Rhbg, 5 mM NH4+ induced an inward I(NH4) of -79 nA, decreased pHi (DeltapHi) by 0.13 at a rate (dpHi/dt) of -2 7 x 10(-4) pH/s and depolarized the cell by 45 mV. These changes were significantly more than those in control oocytes. I-V plots in the presence of NH4+ showed substantial increase in conductance. Amiloride (1 mM) inhibited I(NH4), DeltapHi and dpHi/dt in oocytes expressing Rhbg but not in control oocytes. Raising bath [NH4+] in increments from 1 to 20 mM elicited a faster dpHi/dt, a larger decrease in pHi and a larger depolarization. Net NH4+ flux by Rhbg (estimated from dpHi/dt) was proportional to [NH4+] gradient and followed saturation kinetics with an apparent Km of 2.3 mM. Methyl ammonium (5 mM) induced a current of -63 nA in Rhbg oocytes but did not cause any change in control oocytes. These data indicate that: 1) Rhbg transport of NH4+ is electrogenic. 2) Methyl ammonium is transported by Rhbg. 3) NH4+ transport by Rhbg is saturated at high concentrations with Michaelis-Menten kinetics.
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PMID:Electrogenic ammonium transport by renal Rhbg. 1658 Aug 64


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