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)

It is difficult to correlate structure with function in the kidney because of the extensive cell heterogeneity. Carbonic anhydrase (CA) is an enzyme that mediates renal acidification and is found predominantly in proximal tubule and collecting duct cells. We modified Hansson's method for histochemically identifying cellular CA activity on PLP-fixed rabbit kidney sections mounted on Millipore filters, and then removed the filters to perform peanut lectin and antibody labeling on the same sections. There was adequate preservation of morphology, and individual cells could be identified with CA activity in the cytosol and specific antibody or lectin labeling on the cell surfaces.
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PMID:Novel method for performing carbonic anhydrase histochemistry and immunocytochemistry on cryosections. 137 37

Previous in vitro studies have demonstrated spontaneous bicarbonate absorption in the outer stripe portion of the rat outer medullary collecting duct (OMCD) and inner medullary collecting duct, but net acid transport has not been studied in the inner stripe of the rat OMCD (OMCDIS). When we perfused isolated OMCDIS segments with identical bath and perfusate solutions containing HCO-3 and NH4Cl, HCO-3 was spontaneously absorbed, and total ammonia was spontaneously secreted at rapid rates in tubules from both deoxycorticosterone (DOC)-treated and untreated rats. We next measured the NH3 flux due to imposed NH3 concentration gradients. Carbonic anhydrase (CA), when added to the lumen, enhanced the NH3 flux, implying an absence of endogenous CA. The NH3 permeability was 0.0042 +/- 0.0007 cm/s. By measuring the luminal pH in perfused OMCDIS segments with an imposed lumen-to-bath NH3 gradient, we determined the pH at the end of the lumen to be 0.23 units below the equilibrium pH calculated from the simultaneously measured total CO2 concentration in collected fluid, confirming the lack of luminal CA. These results are consistent with the view that ammonium secretion in the OMCDIS occurs predominantly by H+ secretion and parallel NH3 diffusion. A luminal disequilibrium pH due to H+ secretion in the absence of endogenous luminal CA enhances the NH3 entry rate. Spontaneous net acid secretion appears to occur more rapidly in the OMCD than in other parts of the rat collecting duct system.
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PMID:Ammonium and bicarbonate transport in rat outer medullary collecting ducts. 173 85

The localization of carbonic anhydrase by histochemistry, of Na-K-ATPase by immunocytochemistry and of rod-shaped intramembranous particles by freeze-fracture electron microscopy, was determined in the collecting duct of rabbits. In the cortical collecting duct (CCD), rod-shaped particles, which are abundant in intercalated cells were observed in both the apical and basolateral membrane of all intercalated cells examined. In the outer stripe of the outer medullary collecting duct (OMCDo) a high density of rod-shaped particles was found only in the apical membrane of intercalated cells. All cells of the inner stripe of the outer medullary collecting duct (OMCDi) had rod-shaped particles in the apical membrane but not in the basolateral membrane. As the collecting duct entered the inner medulla the density of rod-shaped particles decreased until they were virtually absent in the terminal segment. Na-K-ATPase, localized to the basolateral membrane, was more abundant in principal cells than in intercalated cells in the CCD. In the OMCDo, staining was equal in principal and intercalated cells. All cells of the OMCDi and the inner medullary collecting duct (IMCD) stained for Na-K-ATPase. Carbonic anhydrase in the CCD was localized to the cell membranes and cytoplasm of intercalated cells. Principal cells did not stain for carbonic anhydrase. A similar pattern was seen in the OMCDo. In the outer region of the OMCDi most cells did not stain for carbonic anhydrase, whereas in the inner region the apical and lateral membranes of all cells stained for carbonic anhydrase. Weak cytoplasmic staining was occasionally seen. A similar pattern was seen in the initial half of the IMCD, while the terminal half of the IMCD did not stain. In this study, the localization of enzymes and rod-shaped intramembranous particles associated with Na+, K+, and H+ transport shows both segmental and cellular heterogeneity, and correlates with the known transport properties of tubule segments. The distribution of these enzymes and rod-shaped intramembranous particles is different in rabbits and rats, and may explain some of the functional differences between homologous segments in these species.
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PMID:Morphological heterogeneity of the rabbit collecting duct. 246 75

Renal oncocytoma is a distinct type of epithelial tumor said to arise from the collecting duct system. Here we show that in nine of ten oncocytomas the tumor cells expressed an analog of the erythrocyte anion exchanger band 3. In the normal kidney band 3 is confined to the basolateral surface of the majority of intercalated cells which comprise up to 50% of the cortical collecting duct epithelium. Carbonic anhydrase c is another protein abundant in intercalated cells, and this was also expressed in six of the ten oncocytomas investigated. Immunoreactivity specific for band 3 and carbonic anhydrase c was not detected in any of the 20 renal cell carcinomas examined. At favourable section planes direct transitions between normal collecting ducts and oncocytic tubules were observed. These findings suggest that oncocytomas may develop from intercalated cells of the collecting duct epithelium.
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PMID:Intercalated cells as a probable source for the development of renal oncocytoma. 246 71

Highly specific antibodies against vital enzymes of the collecting ducts were used to study the appearance of cell type specific enzyme profiles in developing rat kidneys. (Na+K)-ATPase, the abundant enzyme of principal cells, could be detected early in utero in most collecting duct cells. However, the characteristic basolateral polarization of this enzyme did not appear until the first hours after birth. After this, the relative amount of (Na+K)-ATPase immunoreactive cells along collecting ducts decreased steadily, to reach the amount found in adult rat kidneys by the 30th postnatal day. Carbonic anhydrase immunoreactivity characteristic for intercalated cells was not detectable in fetal kidneys, but appeared soon after birth, with steadily increasing numbers of cells that were positive. Interestingly, immunoreactive band 3 glycoprotein (anion channel protein of erythrocytes) did not appear until the 5th day of life, with only a slowly increasing number of cells positive for this probe. These results, showing the sequential appearance of cell type-specific enzyme reactivities along collecting ducts, likely reflect a similar pattern of functional development of the respective main cell types. These results may provide an explanation for physiologic neonatal acidosis, as the enzyme profile associated with proton secretion was seen to appear slowly during the first weeks of life in a distinct manner.
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PMID:Ontogeny of cell type-specific enzyme reactivities in kidney collecting ducts. 282 8

This study was designed to establish the relationship between urinary pCO2 and systemic blood pCO2 during acute hypercapnia and to investigate the significance of this relationship to collecting duct hydrogen ion (H+) secretion when the urine is acid and when it is highly alkaline. In rats excreting a highly alkaline urine, an acute increase in blood pCO2 (from 42 +/- 0.8 to 87 +/- 0.8 mmHg) resulted in a significant fall in urine minus blood (U-B) pCO2 (from 31 +/- 2.0 to 16 +/- 4.2 mmHg, P less than 0.005), a finding which could be interpreted to indicate inhibition of collecting duct H+ secretion by hypercapnia. The urinary pCO2 of rats with hypercapnia, unlike that of normocapnic controls, was significantly lower than that of blood when the urine was acid (58 +/- 6.3 and 86 +/- 1.7 mmHg, P less than 0.001) and when it was alkalinized in the face of accelerated carbonic acid dehydration by infusion of carbonic anhydrase (78 +/- 2.7 and 87 +/- 1.8 mmHg, P less than 0.02). The finding of a urinary pCO2 lower than systemic blood pCO2 during hypercapnia suggested that the urine pCO2 prevailing before bicarbonate loading should be known and the blood pCO2 kept constant to evaluate collecting duct H+ secretion using the urinary pCO2 technique. In experiments performed under these conditions, sodium bicarbonate infusion resulted in an increment in urinary pCO2 (i.e., a delta pCO2) which was comparable in hypercapnic and normocapnic rats (40 +/- 7.2 and 42 +/- 4.6 mmHg, respectively) that were alkalemic (blood pH 7.53 +/- 0.02 and 7.69 +/- 0.01, respectively). The U-B pCO2, however, was again lower in hypercapnic than in normocapnic rats (15 +/- 4.0 and 39 +/- 2.5 mmHg, respectively, P less than 0.001). In hypercapnic rats in which blood pH during bicarbonate infusion was not allowed to become alkalemic (7.38 +/- 0.01), the delta pCO2 was higher than that of normocapnic rats which were alkalemic (70 +/- 5.6 and 42 +/- 4.6 mmHg, respectively, P less than 0.005) while the U-B pCO2 was about the same (39 +/- 3.7 and 39 +/- 2.5 mmHg). We further examined urine pCO2 generation by measuring the difference between the urine pCO2 of a highly alkaline urine not containing carbonic anhydrase and that of an equally alkaline urine containing this enzyme. Carbonic anhydrase infusion to hypercapnic rats that were not alkalemic resulted in a fall in urine pCO(2) (from 122+/-5.7 to 77+/-2.2 mmHg) which was greater (P <0.02) than that seen in alkalemic normocapnic controls (from 73+/- 1.9 to 43+/-1.3 mmHg) with a comparable urine bicarbonate concentration and urine nonbicarbonate buffer capacity. CO(2) generation, therefore, from collecting dust H(+) secretion and titration of bicarbonate, was higher in hypercapnic rats that in normocapnic controls. We conclude that in rats with actue hypercapnia, the U-B p(CO(2)) achieved during bicarbonate loading greatly underestimates collecting duct H(+) secretion because it is artificially influenced by systemic blood pCO(2). the deltapCO(2) is a better qualitative index of collecting duct H+ secretion that the U-B pCO(2), because it is not artificially influenced by systemic blood pCO(2) and it takes into account the urine PCO(2) prevailing before bicarbonate loading.
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PMID:Relationship of urinary and blood carbon dioxide tension during hypercapnia in the rat. Its significance in the evaluation of collecting duct hydrogen ion secretion. 298 5

The criteria upon which diuretics are classified are based upon their site of action within the nephron. Carbonic anhydrase inhibitors act in the proximal tubule, high-ceiling diuretics in the ascending loop of Henle, the thiazides in the early distal tubule and the potassium-sparing diuretics in the late distal tubule and in the collecting duct. According to the localization of carbonic anhydrase acetazolamide acts on three different sites in the proximal tubule cells. The loop diuretics inhibit the secondary active chloride reabsorption. Experiments on the isolated stripped rabbit colon under the condition of stimulated chloride secretion reveal striking similarities between the receptors for chloride reabsorption in the luminal cell membranes of the ascending loop of Henle and in the serosal cell membranes of the colon. The potassium-sparing diuretics act by blocking sodium channels in the distal parts of the nephron. The lumen negative potential difference decreases and potassium secretion is diminished.
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PMID:Diuretic agents: actions on a molecular level. 629 30

Carbonic anhydrase is a zinc metalloenzyme widely distributed throughout the tissues of the body. This enzyme exists in a number of isozymic forms in most mammalian species. Significant advances over the past decade have been made in characterizing the nature of renal carbonic anhydrase. In the kidney, this enzyme is thought to play a pivotal role in urinary acidification and bicarbonate reabsorption. Two distinct isozymes of carbonic anhydrase have now been identified in the mammalian kidney. A soluble cytoplasmic form, similar if not identical to human erythrocyte carbonic anhydrase C, accounts for the bulk of the renal carbonic anhydrase activity. In addition, a membrane-bound form constituting only about 2--5% of the renal activity has been found in the brush border and basolateral fractions of kidney homogenates. The histochemical and immunocytochemical localization of these isozymes along the nephron and collecting duct system of various mammalian species suggests that marked heterogeneity exists. The Editorial Review examines the biochemical and morphological approaches that have been used to elucidate the nature of renal carbonic anhydrase and to assess its distribution along the urinary tubule. Possible physiological roles for the renal carbonic anhydrases are considered for the different segments of the nephron and collecting duct system.
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PMID:Renal carbonic anhydrase. 681 35

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

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


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