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

A mathematical model of the inner medullary collecting duct (IMCD) of the rat has been developed representing Na+, K+, Cl-, HCO3-, CO2, H2CO3, phosphate, ammonia, and urea. Novel model features include: finite rates of hydration of CO2, a kinetic representation of the H-K-ATPase within the luminal cell membrane, cellular osmolytes that are regulated in defense of cell volume, and the repeated coalescing of IMCD tubule segments to yield the ducts of Bellini. Model transport is such that when entering Na+ is 4% of filtered Na+, approximately 75% of this load is reabsorbed. This requirement renders the area-specific transport rate for Na+ comparable to that for proximal tubule. With respect to the luminal membrane, there is experimental evidence for both NaCl cotransport and an Na+ channel in parallel. The experimental constraints that transepithelial potential difference is small and that the fractional apical resistance is greater than 85% mandate that more than 75% of luminal Na+ entry be electrically silent. When Na+ delivery is limited, an NaCl cotransporter can be effective at reducing luminal Na+ concentration to the observed low urinary values. Given the rate of transcellular Na+ reabsorption, there is necessarily a high rate of peritubular K+ recycling; also, given the lower bound on luminal membrane Cl- reabsorption, substantial peritubular Cl- flux must be present. Thus, if realistic limits on cell membrane electrical resistance are observed, then this model predicts a requirement for peritubular electroneutral KCl exit.
 ...
PMID:A mathematical model of the inner medullary collecting duct of the rat: pathways for Na and K transport. 961 21

In tubules from the terminal segment of the inner medullary collecting duct (tIMCD) from rats with chronic metabolic acidosis, our laboratory has shown that bicarbonate absorption (JtCO2) is inhibited by removal of K+ from the luminal fluid or by the addition of Sch-28080 to the perfusate. The present study asked whether total and/or Sch-28080-sensitive JtCO2 is regulated by changes in systemic K+ homeostasis. Rat tIMCD tubules were perfused in vitro in symmetrical, HCO-3/CO2-buffered solutions containing 10 mM KCl + 6 mM NH4Cl. Total and Sch-28080-sensitive JtCO2 were measured in rats with varying K+ intake. In K+-replete rats, baseline JtCO2 was 2.1 +/- 0.3 pmol . mm-1 . min-1 (n = 6). In rats fed a K+-deficient diet for 3 days, JtCO2 was 5.4 +/- 0.7 pmol . mm-1 . min-1 (n = 16, P < 0. 05). To determine the mechanism for the increase in HCO-3 absorption observed with K+ restriction, the Sch-28080-sensitive component of JtCO2 was measured in each treatment group. Following the addition of Sch-28080 (10 microM) to the perfusate, a 40% reduction in JtCO2 was observed in K+-restricted rats. JtCO2 was not reduced following the addition of Sch-28080 in rats with normal K+ intake. Because Sch-28080-sensitive JtCO2 was increased in K+-restricted rats, Sch-28080-sensitive JtCO2 was studied further in tIMCD tubules from rats in this treatment group. In K+-restricted rats, JtCO2 decreased by 20% following the addition of 5 mM ouabain to the perfusate. This ouabain-induced decline in JtCO2 was observed both in the presence and in the absence of Sch-28080. We conclude that total and Sch-28080-sensitive net acid secretion is increased with dietary K+ restriction. However, since approximately 50% of JtCO2 is insensitive to both Sch-28080 and ouabain, future studies will be necessary to define other mechanisms of luminal acidification in the rat tIMCD.
 ...
PMID:Dietary K+ restriction upregulates total and Sch-28080-sensitive bicarbonate absorption in rat tIMCD. 975 26

The cortical collecting duct (CCD) B cell possesses an apical anion exchanger dissimilar to AE1, AE2, and AE3. The purpose of these studies was to characterize this transporter more fully by examining its regulation by CO2 and HCO3. We measured intracellular pH (pHi) in single intercalated cells of in vitro microperfused CCD using the fluorescent, pH-sensitive dye, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF). In the absence of extracellular CO2/HCO3, luminal Cl removal caused reversible intracellular alkalinization, identifying this transporter as a Cl/base exchanger able to transport bases other than HCO3. Adding extracellular CO2/HCO3 decreased B cell pHi while simultaneously increasing Cl/base exchange activity. Since intracellular acidification inhibits AE1, AE2, and AE3, we examined mechanisms other than pHi by which the stimulation occurred. These studies showed that B cell apical anion exchange activity was CO2 stimulated and carbonic anhydrase dependent. Moreover, the stimulation was independent of luminal bicarbonate, luminal pH or pHi, and changes in buffer capacity. We conclude that the B cell possesses an apical Cl/base exchanger whose activity is regulated by CO2-stimulated, carbonic anhydrase-dependent cytoplasmic HCO3 formation.
 ...
PMID:Regulation of B-type intercalated cell apical anion exchange activity by CO2/HCO3-. 984

Mice with a targeted disruption of Na+/H+ exchanger NHE-3 gene show significant reduction in HCO-3 reabsorption in proximal tubule, consistent with the absence of NHE-3. Serum HCO-3, however, is only mildly decreased (P. Schulties, L. L. Clarke, P. Meneton, M. L. Miller, M. Soleimani, L. R. Gawenis, T. M. Riddle, J. J. Duffy, T. Doetschman, T. Wang, G. Giebisch, P. S. Aronson, J. N. Lorenz, and G. E. Shull. Nature Genet. 19: 282-285, 1998), indicating possible adaptive upregulation of HCO-3-absorbing transporters in collecting duct of NHE-3-deficient (NHE-3 -/-) mice. Cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) were perfused, and total CO2 (net HCO-3 flux, JtCO2) was measured in the presence of 10 microM Schering 28080 (SCH, inhibitor of gastric H+-K+-ATPase) or 50 microM diethylestilbestrol (DES, inhibitor of H+-ATPase) in both mutant and wild-type (WT) animals. In CCD, JtCO2 increased in NHE-3 mutant mice (3.42 +/- 0.28 in WT to 5.71 +/- 0.39 pmol. min-1. mm tubule-1 in mutants, P < 0.001). The SCH-sensitive net HCO-3 flux remained unchanged, whereas the DES-sensitive HCO-3 flux increased in the CCD of NHE-3 mutant animals. In OMCD, JtCO2 increased in NHE-3 mutant mice (8.8 +/- 0.7 in WT to 14.2 +/- 0.6 pmol. min-1. mm tubule-1 in mutants, P < 0.001). Both the SCH-sensitive and the DES-sensitive HCO-3 fluxes increased in the OMCD of NHE-3 mutant animals. Northern hybridizations demonstrated enhanced expression of the basolateral Cl-/HCO-3 exchanger (AE-1) mRNA in the cortex. The gastric H+-K+-ATPase mRNA showed upregulation in the medulla but not the cortex of NHE-3 mutant mice. Our results indicate that HCO-3 reabsorption is enhanced in CCD and OMCD of NHE-3-deficient mice. In CCD, H+-ATPase, and in the OMCD, both H+-ATPase and gastric H+-K+-ATPase contribute to the enhanced compensatory HCO-3 reabsorption in NHE-3-deficient animals.
 ...
PMID:HCO-3 reabsorption in renal collecting duct of NHE-3-deficient mouse: a compensatory response. 1036 80

To determine pathways of HCO3- reabsorption in the collecting duct of the mouse kidney, the outer medullary collecting duct (OMCD) and the terminal inner medullary collecting duct (IMCDt) were dissected and perfused at 1 to 2 nL/min, and total CO2 was measured by microfluorometry. In the OMCD, net HCO3- flux (JtCO2) was 12.2 +/- 0.7 pmol/min/mm tubule length and decreased to 6.9 +/- 0.6 pmol/min/mm tubule length (n = 5) with 10 mol/L Schering 28080 (SCH) in perfusate (P < .001) and to 7.7 +/- 0.6 pmol/min/mm tubule length (P < .004; n = 4) with 50 micromol/L diethylstilbestrol (DES), an inhibitor of H+-adenosine triphosphatase; together they reduced JtCO2 to 3.7 +/- 0.2 pmol/min/mm tubule length (P = .0002; n = 4). In IMCDt, JtCO2 was 10.9 +/- 1.1 pmol/min/mm tubule length, and it decreased to 4.3 +/- 0.9 pmol/min/mm tubule length (n = 4) with 10 micromol/L SCH in perfusate (P < .05) and to 7.0 +/- 1.1 pmol/min/mm tubule length (P < .05; n = 4) with 50 micromol/L DES; together they decreased JtCO2 to 2.3 +/- 0.3 pmol/min/mm tubule length (P < .002; n = 4). Ouabain (1 mmol/L), an inhibitor of colonic H-K-adenosine triphosphatase (cHKA), in perfusate had no effect on JtCO2 in either segment. Northern hybridization studies showed a high level of expression of gastric HKA (gHKA) in outer medulla and a low level in inner medulla; cHKA expression was undetectable. Thus, in normal mouse OMCD and IMCDt, HCO3- reabsorption is predominantly mediated by gHKA and H+-adenosine triphosphatase and not cHKA. A third isoform of HKA could be present in mouse IMCDt.
 ...
PMID:Pathways for HCO3-reabsorption in mouse medullary collecting duct segments. 1098

In rat kidney the "secretory" isoform of the Na+-K+-2Cl- cotransporter (NKCC1) localizes to the basolateral membrane of the alpha-intercalated cell. The purpose of this study was to determine whether rat outer medullary collecting duct (OMCD) secretes Cl- and whether transepithelial Cl- transport occurs, in part, through Cl- uptake across the basolateral membrane mediated by NKCC1 in series with Cl- efflux across the apical membrane. OMCD tubules from rats treated with deoxycorticosterone pivalate were perfused in vitro in symmetrical HCO/CO2-buffered solutions. Cl- secretion was observed in this segment, accompanied by a lumen positive transepithelial potential. Bumetanide (100 microM), when added to the bath, reduced Cl- secretion by 78%, although the lumen positive transepithelial potential and fluid flux were unchanged. Bumetanide-sensitive Cl- secretion was dependent on extracellular Na+ and either K+ or NH, consistent with the ion dependency of NKCC1-mediated Cl- transport. In conclusion, OMCD tubules from deoxycorticosterone pivalate-treated rats secrete Cl- into the luminal fluid through NKCC1-mediated Cl- uptake across the basolateral membrane in series with Cl- efflux across the apical membrane. The physiological role of NKCC1-mediated Cl- uptake remains to be determined. However, the role of NKCC1 in the process of fluid secretion could not be demonstrated.
 ...
PMID:Contribution of the Na+-K+-2Cl- cotransporter NKCC1 to Cl- secretion in rat OMCD. 1129 35

The effect of L-arginine on transepithelial ion transport was examined in cultured M-1 mouse renal cortical collecting duct (CCD) cells using continuous short circuit current (Isc) measurements in HCO3-/CO2 buffered solution. Steady state Isc averaged 73.8 +/- 3.2 microA/cm2 (n = 126) and was reduced by 94 +/- 0.6% (n = 16) by the apical addition of 100 microM amiloride. This confirms that the predominant electrogenic ion transport in M-1 cells is Na+ absorption via the epithelial sodium channel (ENaC). Experiments using the cationic amino acid L-lysine (radiolabeled) as a stable arginine analogue show that the combined activity of an apical system y+ and a basal amino acid transport system y+L are responsible for most cationic amino acid transport across M-1 cells. Together they generate net absorptive cationic amino acid flux. Application of L-arginine (10 mM) either apically or basolaterally induced a transient peak increase in Isc averaging 36.6 +/- 5.4 microA/cm2 (n = 19) and 32.0 +/- 7.2 microA/cm2 (n = 8), respectively. The response was preserved in the absence of bath Cl- (n = 4), but was abolished either in the absence of apical Na+ (n = 4) or by apical addition of 100 microM amiloride (n = 6). L-lysine, which cannot serve as a precursor of NO, caused a response similar to that of L-arginine (n = 4); neither L-NMMA (100 microM; n = 3) nor L-NAME (1 mM; n = 4) (both NO-synthase inhibitors) affected the Isc response to L-arginine. The effects of arginine or lysine were replicated by alkalinization that mimicked the transient alkalinization of the bath solution upon addition of these amino acids. We conclude that in M-1 cells L-arginine stimulates Na+ absorption via a pH-dependent, but NO-independent mechanism. The observed net cationic amino acid absorption will counteract passive cationic amino acid leak into the CCD in the presence of electrogenic Na+ transport, consistent with reports of stimulated expression of Na+ and cationic amino acid transporters by aldosterone.
 ...
PMID:L-arginine effects on Na+ transport in M-1 mouse cortical collecting duct cells--a cationic amino acid absorbing epithelium. 1131 95

Carbonic anhydrase (CA) is an important enzyme in the kidney and facilitates renal acidification by catalvzing the reversible hydration of CO2 and the dehydration of bicarbonate. Currently, 14 isoforms of CA have been identified, of which CA II, CA IV, CA XII and possibly CA XIV are expressed by the kidney. Cytosolic CA II comprises -95% of renal CA, with the remainder being membrane-associated. CA II, while being nearly ubiquitous in the body, is also expressed by a large number of nephron segments, including proximal convoluted and straight tubules, thin descending limbs of Henle's loop, thick ascending limbs of Henle's loop in some species, intercalated cells of the cortical and medullary collecting ducts, and weakly in principal cells and inner medullary collecting ducts of some species; CA II is not found in glomeruli. Most membrane-associated CA is attributed to isoform IV, which is linked to the apical membrane via a glycosylphosphatidylinositol anchor; however, there is data showing that CA IV is also localized on the basolateral membranes of proximal tubule cells. How the basolateral form is linked to the membrane is not yet understood. CA IV is expressed on the luminal membrane of proximal convoluted and straight tubules, alpha-intercalated cells of cortical and medullary collecting ducts, and all cells of initial inner medullary collecting ducts. Another membrane isoform, CA XII, is also present in the kidney and probably situated in the basolateral membrane as a single-pass transmembrane protein. One study localizes CA XII to the distal nephron, while another places it in proximal tubules and inner medullary collecting ducts; confirmatory studies are needed for CA XII. The localization of CA XIV in the kidney is still under investigation. Functional studies clearly show the importance of apical and basolateral membrane CAs in mediating bicarbonate and fluid absorption in proximal tubules and of the apical membrane CA activity in mediating H+ secretion in the collecting duct. To establish other roles for CA in the kidney will require further kinetic, functional, immunolocalization and cloning studies.
 ...
PMID:Physiology and molecular biology of renal carbonic anhydrase. 1202 23

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.
 ...
PMID:ANG II reduces net acid secretion in rat outer medullary collecting duct. 1285 Dec 54

The evolutionarily conserved soluble adenylyl cyclase (sAC, adcy10) was recently identified as a unique source of cAMP in the cytoplasm and the nucleus. Its activity is regulated by bicarbonate and fine-tuned by calcium. As such, and in conjunction with carbonic anhydrase (CA), sAC constitutes an HCO(-) 3/CO(-) 2/pH sensor. In both alpha-intercalated cells of the collecting duct and the clear cells of the epididymis, sAC is expressed at significant level and involved in pH homeostasis via apical recruitment of vacuolar H(+)-ATPase (VHA) in a PKA-dependent manner. In addition to maintenance of pH homeostasis, sAC is also involved in metabolic regulation such as coupling of Krebs cycle to oxidative phosphorylation via bicarbonate/CO2 sensing. Additionally, sAC also regulates CFTR channel and plays an important role in regulation of barrier function and apoptosis. These observations suggest that sAC, via bicarbonate-sensing, plays an important role in maintaining homeostatic status of cells against fluctuations in their microenvironment.
...
PMID:Role of the bicarbonate-responsive soluble adenylyl cyclase in pH sensing and metabolic regulation. 2457 49


<< Previous 1 2 3 4 5 6 7 8 Next >>