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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal correction of chloride-depletion alkalosis (CDA) by chloride replacement results in bicarbonate secretion in the cortical collecting duct (CD) and urinary bicarbonate excretion. To assess the participation of the more distal segments of the CD, we determined net total CO2 transport in the outer medullary (OMCD), initial (IMCDi) and terminal (IMCDt) inner medullary CD segments obtained from Sprague-Dawley rats with normal acid-base balance (NML) or with CDA produced by peritoneal dialysis. Tubules were bathed and perfused with isotonic solutions containing Cl 110 mM and HCO, 25 mM. Net total CO2 transport was decreased in all segments: OMCD 22.1 +/- 4.2 to 9.2 +/- 2.0; IMCDi 38.1 +/- 4.6 to 9.3 +/- 1.7; IMCDt 6.7 +/- 1.2 to -0.5 +/- 0.4 pmol/min/mm tubule length. Perfusion rates, tubule lengths, and transepithelial voltages did not differ between groups in any segment. These data show that all CD segments beyond the cortical segment decrease bicarbonate reabsorption during CDA. This permits the bicarbonate secreted by the cortical CD to be excreted, and is likely an important mechanism for the correction of CDA.
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PMID:Bicarbonate transport in collecting duct segments during chloride-depletion alkalosis. 756 91

At least two cortical collecting duct (CCD) intercalated cell populations mediate HCO3- secretion and reabsorption. The present study examined the membrane location of intercalated cell Cl-/base exchange activity and the axial distribution of CCD intercalated cells. CCD were studied using in vitro microperfusion in CO2/HCO3(-)-containing solutions; intracellular pH was measured using 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. The A-type intercalated cell (A cell) and B-type intercalated cell (B cell) were identified functionally by the absence and presence of apical Cl-/HCO3- exchange activity, respectively. When a 0 mM Cl-, 0 mM HCO3- luminal solution was used, removal of Cl- from the peritubular solution caused intracellular alkalinization in all B cells. The alkalinization required neither extracellular Na+ nor changes in membrane potential. Peritubular 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) (10(-4) M) inhibited A cell but not B cell basolateral Cl-/base exchange activity. In comparison to studies performed with a 0 mM Cl- 0 mM HCO3- luminal solution, the use of a 0 mM Cl-, 25 mM HCO3- luminal solution inhibited both the identification and the magnitude of B cell basolateral Cl-/base exchange activity. When CCD from the inner and outer cortex were separately studied, only 7% of outer CCD intercalated cells were A cells, whereas 93% were B cells. In contrast, in the inner CCD, 58% of intercalated cells were A cells and 42% were B cells. Under stop-flow conditions, outer CCD alkalinized the luminal fluid, whereas inner CCD acidified the luminal fluid. These results indicate that all CCD intercalated cells possess basolateral Cl-/base exchange activity; however, A cell and B cell basolateral Cl-/base exchange activity differs, at least in terms of sensitivity to DIDS. Furthermore, there is axial heterogeneity in both intercalated cell type and function.
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PMID:Distribution of Cl-/HCO3- exchange and intercalated cells in rabbit cortical collecting duct. 781 Jul 3

The K+ channels of the principal cells of rat cortical collecting duct (CCD) are pH sensitive in excised membranes. K+ secretion is decreased with increased H+ secretion during acidosis. We examined whether the pH sensitivity of these K+ channels is present also in the intact cell and thus could explain the coupling between K+ and H+ secretion. Membrane voltages (Vm), whole-cell conductances (gc), and single-channel currents of K+ channels were recorded from freshly isolated CCD cells or isolated CCD segments with the patch-clamp method. Intracellular pH (pHi) was measured using the pH-sensitive fluorescent dye 2'-7'-bis(carboxyethyl)-5-6-carboxyfluorescein (BCECF). Acetate (20 mmol/l) had no effect on Vm, gc, or the activity of the K+ channels in these cells. Acetate, however, acidified pHi slightly by 0.17 +/- 0.04 pH units (n = 19). Vm depolarized by 12 +/- 3 mV (n = 26) and by 23 +/- 2 mV (n = 66) and gc decreased by 26 +/- 5% (n = 13) and by 55 +/- 5% (n = 12) with 3-5 or 8-10% CO2, respectively. The same CO2 concentrations decreased pHi by 0.49 +/- 0.07 (n = 15) and 0.73 +/- 0.11 pH units (n = 12), respectively. Open probability (Po) of all four K+ channels in the intact rat CCD cells was reversibly inhibited by 8-10% CO2. pHi increased with the addition of 20 mmol/l NH4+/NH3 by a maximum of 0.64 +/- 0.08 pH units (n = 33) and acidified transiently by 0.37 +/- 0.05 pH units (n = 33) upon NH4+/NH3 removal. In the presence of NH4+/NH3 Vm depolarized by 16 +/- 2 mV (n = 66) and gc decreased by 26 +/- 7% (n = 16). The activity of all four K+ channels was also strongly inhibited in the presence of NH4+/NH3. The effect of NH4+/NH3 on Vm and gc was markedly increased when the pH of the NH4+/NH3-containing solution was set to 8.5 or 9.2. From these data we conclude that cellular acidification in rat CCD principal cells down-regulates K+ conductances, thus reduces K+ secretion by direct inhibition of K+ channel activity. This pH dependence is present in all four K+ channels of the rat CCD. The inhibition of K+ channels by NH4+/NH3 is independent of changes in pHi and rather involves an effect of NH3.
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PMID:pH dependence of K+ conductances of rat cortical collecting duct principal cells. 783 86

These studies examine the effect of ambient PCO2 on net bicarbonate (total CO2) absorption by the in vitro perfused cortical collecting duct (CCD) from K-replete rabbits and the mechanism responsible for this effect. Exposure to 10% CO2 increased net bicarbonate flux (total CO2 flux, JtCO2) by 1.8-fold (P < 0.005), and this effect was inhibited by luminal 10 microM Sch-28080, an H-K-adenosinetriphosphatase (H-K-ATPase) inhibitor. In contrast, exposure to 10% CO2 significantly decreased Rb efflux, and this decrement in Rb efflux was blocked by luminal 2 mM Ba, a K channel blocker. Thus transepithelial tracer Rb flux did not increase upon exposure to 10% CO2 as we have observed in this segment under K-restricted conditions. The observation that 10% CO2 increased net bicarbonate absorption without a change in absorptive Rb flux suggested that 10% CO2 increased apical K recycling. To test this hypothesis, we examined whether luminal Ba inhibited the stimulation of luminal acidification induced by 10% CO2. If apical K exit were necessary for full activation of proton secretion, then inhibiting K exit should indirectly affect the stimulation of JtCO2 by 10% CO2. In fact, the effect of 10% CO2 on JtCO2 in the presence of 2 mM luminal Ba was quantitatively indistinguishable from the effect of 10% CO2 on JtCO2 in the presence of 10 microM luminal Sch-28080.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of total CO2 flux by 10% CO2 in rabbit CCD: role of an apical Sch-28080- and Ba-sensitive mechanism. 804 50

We have previously demonstrated that basolateral addition of the gastric H-K-adenosinetriphosphatase (H-K-ATPase) inhibitor Sch-28080 (10 microM) profoundly reduced net total CO2 flux (JtCO2) in the inner stripe of the outer medullary collecting duct (OMCDi) of K-replete rabbits. In the present studies, we first addressed whether the inhibitory effect of Sch-28080 is dependent on the side of the membrane to which it is added. Second, we reassessed the relative magnitude of contribution of H-K-ATPase. Third, we formally tested whether a bafilomycin-A1 (BAF)-sensitive H-ATPase also contributes to luminal acidification in the OMCDi under K-replete dietary conditions. We found that luminal addition of the structurally and functionally dissimilar gastric H-K-ATPase inhibitor A80915A (10 microM) profoundly reduced JtCO2 while transepithelial voltage (VT) was unchanged. This degree of inhibition was statistically indistinguishable from our previous results when Sch-28080 was applied basolaterally. Inhibition of JtCO2 by the less membrane-permeable N-methyl cation of Sch-28080, H224/25, was significant when applied luminally but was not significant when applied basolaterally. VT was not significantly affected by either the luminal or basolateral addition of H224/25. To evaluate the possible contribution of an H-ATPase, the effect of both 5.0 nM and 10.0 nM luminal BAF on JtCO2 and VT was examined. At 5.0 nM, BAF significantly inhibited JtCO2). However, this observation was significantly less (P < 0.05) than the inhibition observed with 10 microM A80915A. No additional inhibition was observed by increasing the concentration of BAF to 10.0 nM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Luminal acidification in K-replete OMCDi: contributions of H-K-ATPase and bafilomycin-A1-sensitive H-ATPase. 809 59

Carbonic anhydrase (CA) facilitates the secretion of protons from renal epithelia by catalyzing the buffering of hydroxyl ions by CO2. We have previously found that inner medullary collecting duct (IMCD) cells cultured from rat kidney secrete protons and express CA II. Incubation of IMCD cells in acidic medium for 48 h has been shown to stimulate the secretion of protons by a protein synthesis-dependent process. To establish whether CA II might be involved in this process, IMCD cells were exposed to incubation media supplemented with 10(-7) M deoxycorticosterone acetate, pH 7.0 (acid) or pH 7.7 (control) for 48 h, and CA II mRNA and protein were quantitated. Part of the CA II cDNA was obtained by reverse transcription of total RNA from rat kidney followed by amplification using oligonucleotide primers derived from conserved areas in the coding regions of human, mouse, and chick CA II cDNAs in a polymerase chain reaction. By Northern analysis, steady-state levels of CA II mRNA from acid-incubated cells showed an increase of 80% compared with controls and 70% when expressed relative to a housekeeping mRNA, beta-actin. Western blot analysis using a human antibody to CA II showed an approximate doubling of CA II protein after acid incubation. By immunofluorescence microscopy, the domes of acid-incubated IMCD cells contained considerably more CA II-stained cells than found in control cultures. Thus incubation of IMCD cells in acid medium stimulates the expression of CA II mRNA and protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Low pH enhances expression of carbonic anhydrase II by cultured rat inner medullary collecting duct cells. 814 Dec 64

The inner medullary collecting duct (IMCD) is the final portion of the mammalian renal tubule that is able to significantly regulate systemic acid-base balance. Although the H+ transporters of this segment are relatively well studied, little is known regarding the mechanisms of HCO3- transport. The mechanisms of HCO3- transport in primary cultures of rabbit IMCD were studied using the pH-sensitive dye, 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, in CO2/HCO3(-)-containing solutions at 37 degrees C. Removal of Cl- from the extracellular solution caused reversible intracellular alkalinization, demonstrating the presence of Cl-/HCO3- exchange. Alkalinization with Cl- removal was independent of changes in membrane potential, did not require the presence of extracellular Na+, and was inhibited by the disulfonic stilbene, 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 10(-4) M). Half-maximal intracellular pH (pHi) recovery with readdition of Cl- to the extracellular solution occurred at a Cl- concentration of 37.4 +/- 5.7 mM. When rabbit IMCD were cultured on permeable support membranes, Cl-/HCO3- exchange activity was found only on the basolateral membrane. However, there was no evidence of band 3 protein immunoreactivity. In contrast, no evidence for Na(+)-(HCO3-)n > 1 cotransport activity was found. Depolarization of IMCD cells by acute increases in extracellular K+ did not alter pHi, nor was Na(+)-dependent, 5-(N-ethyl-N-isopropyl)amiloride-insensitive pHi recovery from an acid load inhibited by DIDS (10(-4) M). Finally, recovery from intracellular alkalosis induced by incubation in 0 mM Cl-, 50 mM HCO3- extracellular solution required Cl- and was independent of Na+. These studies indicate that the major mechanism of HCO3- transport in primary cultures of the rabbit IMCD is via a band 3 protein-negative, Na(+)-independent, basolateral, Cl-/HCO3- exchanger.
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PMID:Mechanisms of bicarbonate transport by cultured rabbit inner medullary collecting duct cells. 816 Jul 96

The inner stripe of the outer medullary collecting duct (OMCDis) is a major site of HCO3- reabsorption and urinary acidification. Whether this nephron segment consists of a single or multiple cell types remains unclear. Apical incubation of rabbit OMCDis via luminal perfusion with 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester resulted in heterogeneous fluorescence, suggesting two cell types. This heterogeneity was not prevented by inhibition of either carbonic anhydrase or organic anion transport. Subsequent studies were directed at characterizing the major intracellular pH (pHi) regulatory transporters in these two cell populations. Both cell populations demonstrated similar rates of Na+/H+ exchange, as assessed by peritubular Na(+)-dependent, amiloride-sensitive pHi recovery from an intracellular acid load. In contrast, Na(+)-independent, HCO3(-)-independent pHi recovery from an acid load was present in both cell populations but had two to three times greater activity in a minority cell population. In vivo deoxycorticosterone acetate administration increases this rate in both populations but to a greater extent in the minority cell population. In CO2/HCO3(-)-containing solutions, Cl- removal from the peritubular solution caused 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid-sensitive alkalinization of all cells. Again, the magnitude and rate of alkalinization were significantly greater in the minority cell population. These studies demonstrate that the OMCDis consists of qualitatively similar cells in different states of functional activity. Although they are similar in most characteristics, a minority of cells more actively secrete H+ (independent of Na+) and reabsorb HCO3-.
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PMID:Regulation of intracellular pH in two cell populations of inner stripe of rabbit outer medullary collecting duct. 821

Carbonic anhydrase II (CA II), the predominant isoform of carbonic anhydrase in the kidney, is believed to be localized primarily in the cytoplasm of proximal tubule and collecting duct intercalated cells. Carbonic anhydrase facilitates H+ secretion by catalyzing the formation of HCO3- from OH- in the presence of CO2. We have shown that renal cortical CA II activity is stimulated during 4-6 days of chronic metabolic acidosis [L.P. Brion, B.J. Zavilowitz, O. Rosen, and G.J. Schwartz. Am. J. Physiol. 261 (Regulatory Integrative Comp. Physiol. 30): R1204-R1213, 1991]. The purpose of these studies was to examine under similar conditions the regulation of CA II mRNA. We obtained a major portion of the rabbit CA II cDNA by reverse transcription of total RNA from rabbit kidney followed by amplification using oligonucleotide primers prepared from conserved areas in the coding regions of human, mouse, and chick CA II cDNAs in a polymerase chain reaction (RT-PCR). The 696-bp RT-PCR product was sequenced and found to be 71-86% homologous to CA II cDNAs from the other three species. The deduced amino acid sequence agreed closely (> 97%) with a previous Edman analysis of rabbit erythrocyte CA II. Northern analysis showed expression of a approximately 1.4 kb RNA, with cortex > outer medulla > inner medulla. Steady-state mRNA expression from kidney cortex of acid-treated rabbits was about twice that from controls, when normalized to the expression of beta-actin or malate dehydrogenase. The stimulation of CA II mRNA was greater after 3 days than after 5-6 days of acid treatment. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carbonic anhydrase II mRNA is induced in rabbit kidney cortex during chronic metabolic acidosis. 828 9

In the rat cortical collecting duct (CCD), the presence of highly specific receptors to calcitonin (CT) coupled to a sensitive adenylate cyclase system suggests that this segment is a target site for CT. Our aim was to explore the effects of CT on the rat CCD microperfused in vitro. The hormone failed to alter the osmotic water permeability and did not affect net Na+ transport but generated a lumen-positive transepithelial potential difference (PDte), which under control conditions was close to zero. This response was dose dependent and was still observed in the presence of luminal amiloride, despite the luminal positivity generated by the Na+ channel blocker (PDte increased from 4.0 +/- 0.8 to 9.5 +/- 1.1 mV). In contrast, the nominal absence of CO2/HCO3- or the use of a low-Cl- solution totally prevented the PDte changes caused by CT. The CT-induced lumen-positive PDte was reduced by 2.3 +/- 0.8 mV after the basolateral addition of the Cl- channel inhibitor diphenylamine-2-carboxylate. 4-Acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid and acetazolamide, which inhibit Cl-/HCO3- exchangers and carbonic anhydrase activities, respectively, also inhibited the CT-induced PDte by 4.6 +/- 0.5 and 5.0 +/- 0.9 mV. To test whether the acid-base status of the animals influences the response to CT, rats underwent an acid or alkali load. CCD dissected from acid-loaded rats responded to CT to the same extent as control animals, but the hormonal action was significantly attenuated when the CCD was harvested from alkali-loaded rats (PDte increases: acid 4.0 +/- 0.3 vs. alkali 1.6 +/- 0.6 mV, P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of calcitonin on function of intercalated cells of rat cortical collecting duct. 844 35


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