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)

We investigated the tubular action of endothelin in rat nephron segments. The effects of endothelin on arginine vasopressin (AVP)-, parathyroid hormone-, glucagon-, calcitonin-, and isoproterenol-dependent cAMP accumulation were studied. The following nephron segments were microdissected: glomerulus (Gl), proximal convoluted tubule (PCT), cortical and medullary thick ascending limbs of Henle's loop (cTAL and mTAL, respectively), cortical collecting duct (CCD), outer medullary collecting duct (OMCD), and inner medullary collecting duct (IMCD). Endothelin dose dependently (10(-8)-10(-10)M) inhibited AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD. This effect was independent of the presence or absence of phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, Ca channel blocker nicardipine, or indomethacin, but was abolished in the presence of protein kinase C inhibitor H-7. Protein kinase C stimulator dioctanoyl glycerol mimicked the effect of endothelin. On the other hand, endothelin had no inhibitory effect on AVP-dependent cAMP accumulation in cTAL or mTAL, parathyroid hormone-dependent cAMP accumulation in Gl and PCT, or glucagon-, calcitonin-, and isoprotereol-dependent cAMP accumulation in OMCD. We conclude that endothelin specifically inhibits AVP-dependent cAMP accumulation in CCD, OMCD, and IMCD through activating protein kinase C. This effect possibly has a role in maintaining urine volume to counteract the decrease in GFR caused by endothelin itself.
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PMID:Effects of endothelin on peptide-dependent cyclic adenosine monophosphate accumulation along the nephron segments of the rat. 169 79

In this study we investigated the role of protein kinases in activation of the Na(+)-H+ exchanger in inner medullary collecting duct (IMCD) cells. Monolayers, 24-48 h after achieving confluence, were made quiescent by 24 h incubation in 0.1% serum before study. Changes in pHi were measured with 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. Phorbol myristate acetate (PMA), a synthetic analogue of diacylglycerol (DAG), was used to stimulate protein kinase C (PKC). In nominally HCO3(-)-free media containing 110 mM Na+ and 1 mM Ca2+, PMA addition increased pHi from 7.29 +/- 0.08 to 7.54 +/- 0.07 after 20 min. The increment in pHi was completely inhibited by 1 mM amiloride or by replacement of extracellular Na+ with choline but not inhibited by 1 mM N-ethylmaleimide, an inhibitor of active proton transport. Downregulation of PKC by overnight incubation of monolayers with PMA also prevented the rise in pHi upon subsequent challenge with PMA. Another active analogue of DAG, 1,2-dioleoyl-rac-glycerol, caused an increment in pHi similar to that produced by PMA, whereas 4 alpha-phorbol, an inactive analogue, did not stimulate Na(+)-H+ exchange. Bradykinin (10(-6) M), a phospholipase C-activating hormone, also induces alkalinization of IMCD cells similar to that produced by phorbol esters. Neither vasopressin (10(-7) M), which induces cellular accumulation of adenosine 3',5'-cyclic monophosphate (cAMP) and activation of protein kinase A (PKA), nor 8-bromo-cAMP (1 mM) changed pHi. Therefore in the IMCD cell activation of PKC but not PKA stimulates a rise in pHi via the Na(+)-H+ exchanger.
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PMID:Na(+)-H+ exchange is stimulated by protein kinase C activation in inner medullary collecting duct cells. 217 60

Taking into account recent results obtained with isolated papillary collecting duct cells the metabolic pathways and membrane transport systems of collecting duct cells are reviewed. The plasma membranes contain a luminal proton AT-Pase and a contraluminal Cl-/HCO3- exchanger which are involved in proton secretion; a luminal sodium channel and a contraluminal Na+/K+-AT-Pase for sodium reabsorption; a K+ channel for potassium secretion, and a Na+/K+/Cl- cotransport system for chloride transport and/or volume regulation. The plasma membranes also possess transport systems for organic substrates and organic osmolytes. D-glucose, the main substrate of the papillary collecting duct is taken up into the cell by a sodium-independent D-glucose transport system with a Km of 1.2 mM. The plasma membrane also contains mechanisms which mediate sorbitol release into the medium. This mechanism is stimulated when cells are exposed to media with a low osmolality and inhibited when cells are exposed to media with a high osmolality. D-glucose is used as metabolic substrate in anaerobic and aerobic glycolysis and as precursor for sorbitol synthesis via the aldose reductase, which is highly enriched in papillary collecting duct cells. The cells also show gluconeogenic activity as evidenced by incorporation of labeled carbon from L-alanine into glycerol, sorbitol, and myo-inositol. Accordingly, the cells show fructose-1,6-biphosphatase activity. Sorbitol synthesis in contrast to sorbitol permeability is not affected by osmolarity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Transport mechanisms and metabolic processes in isolated cells of the collecting tubule of the kidney papilla]. 284 46

Antidiuretic hormone (ADH) causes the appearance of water-conducting particle aggregates in the luminal membrane of receptor cells in amphibian bladder and skin, and in the mammalian collecting duct. The aggregates originate from cytoplasmic tubules that fuse with the luminal membrane during ADH stimulation. We have studied the process of fusion and the structure of the particle aggregates by a rapid-freeze technique that renders chemical fixation and glycerol protection unnecessary. Our findings differ in some important respects from previously published work. Aggregate particles, in our study, partition equally between the external (EF) and protoplasmic (PF) membrane leaflets, rather than remaining in the protoplasmic leaflet exclusively. By including the entire population of fusion images in our survey, we have found that aggregate delivery in ADH-treated cells proceeds preferentially from small fusion images whose diameter is significantly less than the 0.12 micron characteristic of the carrier tubules themselves. We have also found that, even in unstimulated preparations, fusion images are numerous, being mostly of small diameter. ADH stimulation produces a moderate increase in the number of fusion images and a significant increase in fusion-image diameter. These findings indicate that the individual particles are mobile within the membrane, lacking interparticle linkage. In addition, contact of cytoplasmic tubules with the luminal membrane may take place even in the absence of ADH, producing small fusion images which are not associated with aggregate delivery to the luminal membrane.
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PMID:Fusion images and intramembrane particle aggregates during the action of antidiuretic hormone. A rapid-freeze study. 392 22

Water transport in highly water-permeable membranes is conducted by water-selective pores--namely, water channels. The recent cloning of water channels revealed the water-selective characteristics of these proteins when expressed in Xenopus oocytes or reconstituted in liposomes. Currently, it is assumed that the function of water channels is to transport only water. We now report the cloning of a member of the water channel that also transports nonionic small molecules such as urea and glycerol. We named this channel aquaporin 3 (AQP3) for its predominant water permeability. AQP3 has amino acid sequence identity with major intrinsic protein (MIP) family proteins including AQP-channel-forming integral membrane protein, AQP-collecting duct, MIP, AQP-gamma tonoplast intrinsic protein, nodulin 26, and glycerol facilitator (33-42%). Thus, AQP3 is an additional member of the MIP family. Osmotic water permeability of Xenopus oocytes measured by videomicroscopy was 10-fold higher in oocytes injected with AQP3 transcript than with water-injected oocytes. The increase in osmotic water permeability was inhibited by HgCl2, and this effect was reversed by a reducing agent, 2-mercaptoethanol. Although to a smaller degree, AQP3 also facilitated the transport of nonionic small solutes such as urea and glycerol, while the previously cloned water channels are permeable only to water when expressed in Xenopus oocytes. AQP3 mRNA was expressed abundantly in kidney medulla and colon. In kidney, it was exclusively immunolocalized at the basolateral membrane of collecting duct cells. AQP3 may function as a water and urea exit mechanism in antidiuresis in collecting duct cells.
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PMID:Molecular cloning and expression of a member of the aquaporin family with permeability to glycerol and urea in addition to water expressed at the basolateral membrane of kidney collecting duct cells. 751 46

Two water channel homologs were cloned recently from rat kidney, mercurial-insensitive water channel (MIWC) and glycerol intrinsic protein (GLIP). Polyclonal antibodies were raised against synthetic C-terminal peptides and purified by affinity chromatography. MIWC and GLIP antibodies recognized proteins in rat kidney with an apparent molecular mass of 30 and 27 kDa, respectively, and did not cross-react. By immunofluorescence, MIWC and GLIP were expressed together on the basolateral plasma membrane of collecting duct principal cells in kidney. By immunohistochemistry, MIWC and GLIP were expressed on tracheal epithelial cells with greater expression of GLIP on the basal plasma membrane and MIWC on the lateral membrane; only MIWC was expressed in bronchial epithelia. In eye, GLIP was expressed in conjunctival epithelium, whereas MIWC was found in iris, ciliary body, and neural cell layers in retina. MIWC and GLIP colocalized on the basolateral membrane of villus epithelial cells in colon and brain ependymal cells. Expression of MIWC and GLIP was not detected in small intestine, liver, spleen, endothelia, and cells that express water channels CHIP28 or WCH-CD. These studies suggest water/solute transporting roles for MIWC and GLIP in the urinary concentrating mechanism, cerebrospinal fluid absorption, ocular fluid balance, fecal dehydration, and airway humidification. The unexpected membrane colocalization of MIWC and GLIP in several tissues suggests an interaction at the molecular and/or functional levels.
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PMID:Immunolocalization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes. 753 65

Several membranes of the kidney are highly water permeable, thereby enabling this organ to retain large quantities of water. Recently, the molecular identification of water channels responsible for this high water permeability has finally been accomplished. At present, four distinct renal water channels have been identified, all members of the family of major intrinsic proteins. Aquaporin 1 (AQP1), aquaporin 2 (AQP2) and the mercury-insensitive water channel (MIWC) are water-selective channel proteins, whereas the fourth, referred to as aquaporin 3 (AQP3), permits transport of urea and glycerol as well. Furthermore, a putative renal water channel (WCH3) has been found. AQP1 is expressed in apical and basolateral membranes of proximal tubules and descending limbs of Henle, AQP2 predominantly in apical membranes of principal and inner medullary collecting duct cells and AQP3 in basolateral membranes of kidney collecting duct cells. MIWC is expressed in the inner medulla of the kidney and has been suggested to be localised in the vasa recta. The human genes encoding AQP1 and AQP2 have been cloned, permitting deduction of their amino acid sequence, prediction of their two-dimensional structure by hydropathy analysis, speculations on their way of functioning and DNA analysis in patients with diseases possibly caused by mutant aquaporins. Mutations in the AQP1 gene were recently detected in clinically normal individuals, a finding which contradicts the presumed vital importance of this protein. Mutations in the AQP2 gene were shown to cause autosomal recessive nephrogenic diabetes insipidus. The renal unresponsiveness to arginine vasopressin, which characterises this disease, is in accordance with the assumption that AQP2 is the effector protein of the renal vasopressin pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Discovery of aquaporins: a breakthrough in research on renal water transport. 754 Aug 50

A rapid passive urea transport has been previously described in the mammalian renal inner medullary collecting duct epithelial cells and in mammalian erythrocytes. Recently, a vasopressin-regulated urea transporter (UT2) has been cloned from a rabbit kidney medullary cDNA library (You, G., Smith, C. P., Kanai, Y., Lee, W. S., Stelzner, M., and Hediger, M. A. (1993) Nature 365, 844-847). We now report the cloning and characterization of a complementary DNA (HUT11) encoding an urea transporter isolated from a human bone marrow library. It encodes a 43,000-Da polypeptide of 391 amino acids that exhibited 63% sequence identity with the rabbit urea transporter and a similar membrane topology. HUT11 carries 2 putative glycosylation sites and 10 cysteines, of which only 7 are conserved at an equivalent position in UT2. HUT11 transcripts have been identified in human erythroid and renal tissues. Expression studies in Xenopus oocytes demonstrated that HUT11 mediates a facilitated urea transport that was inhibited, as described in mammalian erythrocytes, by very low concentrations of phloretin, p-chloromercuribenzene sulfonate, and urea analogues. No unidirectional movements of charged molecules, glycerol, or water were associated with HUT11 expression in oocytes. These findings suggest that HUT11 is most likely responsible for the facilitated urea transport in human red blood cells.
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PMID:Cloning and functional expression of a urea transporter from human bone marrow cells. 798 37

In searching for a basolateral membrane water transporter in rat kidney with homology to channel forming integral protein (CHIP28), water channel-collecting duct (WCH-CD), and mercurial-insensitive water channel (MIWC), we cloned a new member of the major intrinsic protein family (GLIP, GLycerol Intrinsic Protein). GLIP cDNA had an 855-base pair open reading frame encoding a 30.5-kDa protein with 19-23% amino acid identity to the water channels and 36% identity to the bacterial glycerol facilitator GlpF. Northern blot analysis showed a 5.5-kilobase mRNA encoding GLIP in kidney, brain, and lung; RT-PCR/Southern blot analysis indicated expression of GLIP in kidney, brain, lung, eye, colon, stomach, and skeletal muscle, but not in heart, liver, and spleen. In situ hybridization in rat kidney showed GLIP mRNA expression in medullary collecting duct. Immunofluorescence with a peptide-derived polyclonal antibody showed GLIP protein expression in basolateral membrane of kidney collecting duct principal cells and brain meningeal cells. Functional measurements in Xenopus oocytes expressing GLIP cRNA showed a > 20-fold increase in [3H]glycerol uptake compared with water-injected oocytes; glycerol uptake was inhibited 88% by diisothiocyanodisulfonic stilbene (0.2 mM) and 36% by phloretin (0.25 mM). GLIP did not function as a transporter for water, urea, inositol, glucose, lactate, and monovalent ions. Glycerol uptake in oocytes expressing CHIP28 and MIWC was not different from that in water-injected controls. GLIP represents the first mammalian water channel homolog that selectively transports a solute other than water. The physiological substrate(s) and role(s) of GLIP remain to be elucidated.
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PMID:Cloning of a water channel homolog expressed in brain meningeal cells and kidney collecting duct that functions as a stilbene-sensitive glycerol transporter. 806 28

Renal collecting duct and thick ascending limb, as well as stomach, exhibit strikingly low permeabilities to water and solutes. However, the apical membrane characteristics responsible for these unique permeabilities remain unknown. While the lipid composition of artificial membranes governs membrane permeability, exoplasmic and cytoplasmic leaflets of biological apical membranes exhibit striking asymmetries in lipid composition. This asymmetry, as well as the presence of membrane proteins, may be critical to barrier function. To determine the role of bulk lipid composition in apical membrane barrier function, we compared permeabilities to water (Pf), protons, ammonia, and several small nonelectrolytes of gastric apical membrane vesicles [native gastric vesicles (NGV)] and liposomes prepared from lipids quantitatively extracted from these vesicles [gastric lipid large unilamellar vesicles (LUV)]. Permeabilities were measured on a stopped-flow fluorimeter by monitoring self- or pH-sensitive quenching of entrapped carboxyfluorescein. NGV exhibited low Pf (2.8 +/- 0.3 x 10(-4) cm/s) while gastric lipid LUV Pf averaged 1.2 +/- 0.1 x 10(-3) cm/s, a fourfold increase compared with the value in NGV. Gastric lipid LUV also demonstrated higher permeabilities to protons, ammonia, propylene glycol, butyramide, ethanolamine, and acetamide compared with values in NGV. In contrast, gastric lipid LUV exhibited the same or lower permeabilities to urea, glycerol, and ammonia compared with values in NGV. We conclude that lipid composition alone can reconstitute membrane permeabilities to some, but not all, molecules. These results indicate that bilayer asymmetry may be required for the unique permeability of "water-tight" apical membranes and reveal different barrier mechanisms for water and protons, as opposed to ammonia, urea, and glycerol.
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PMID:Determinants of apical membrane permeabilities of barrier epithelia. 807 73


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