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)

The vasopressin-dependent urea permeability of the rat terminal inner medullary collecting duct (IMCD) is much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of vasopressin-stimulated facilitated transport pathway. We used the isolated perfused tubule technique to test whether the urea transport pathway exhibits saturation characteristics consistent with a facilitated pathway. When the luminal urea concentration was varied between 0 and 800 mM (no urea in peritubular bath), the relationship between the urea flux and the luminal concentration was linear with a y-axis intercept that was not significantly different from zero, indicating an absence of saturation in this concentration range. Higher concentrations of urea could not be tested due to technical limitations. However, when thiourea (a urea analogue that shares the urea transport pathway with urea) was substituted for urea in similar experiments, the apparent thiourea permeability fell with increasing thiourea concentration in the range 10-200 mM, indicative of saturation of the urea-thiourea transporter. When the urea concentration was varied in both bath and lumen, the lumen-to-bath urea flux approached a limiting value at 400-500 mM urea, consistent with saturation of the transporter. However, nonspecific inhibition of urea transport by bath urea could not be ruled out in those experiments. We conclude that the urea and thiourea transport pathway in the terminal IMCD exhibits saturation characteristics. However, the urea concentration required to saturate the pathway is apparently high, at least 400-500 mM in one set of experiments and probably greater than 800 mM in another.
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PMID:Concentration dependence of urea and thiourea transport in rat inner medullary collecting duct. 210 58

The inner medullary collecting duct (IMCD) is thought to be a major target site for atrial natriuretic factor (ANF) action. The IMCD is divided into two subsegments (IMCD1, outer third; and IMCD2,3, inner two-thirds) based on differences in urea and water permeability. IMCD1 has similar characteristics to the outer medullary collecting duct (OMCD). To elucidate whether there are any differences among these segments in ANF actions, we investigated the effects of ANF on guanosine 3',5'-cyclic monophosphate (cGMP) synthesis in IMCD subsegments and the OMCD. We also examined the effects of arginine vasopressin (AVP) on adenosine 3',5'-cyclic monophosphate (cAMP) synthesis. IMCD subsegments (IMCD1,2,3) and OMCD were microdissected; and ANF-stimulated cGMP synthesis and AVP-stimulated cAMP synthesis were measured. cGMP synthesis stimulated by 10(-6) M ANF in IMCD1,2,3 (0.78 +/- 0.15, 0.81 +/- 0.19, 0.62 +/- 0.10 fmol.mm-1 x 3 min-1, mean +/- SE respectively, n = 10-11) was significantly (greater than 20-fold) higher than that in OMCD (0.03 +/- 0.02 fmol.mm-1 x 3 min-1, n = 7), and there was no difference among IMCD subsegments. On the other hand, cAMP synthesis stimulated by 10(-7) M AVP in IMCD subsegments was similar to that in OMCD. We conclude that IMCD is homogenous as a target site of ANF and is clearly distinguished from OMCD. In addition, more than half of ANF-stimulated cGMP synthesis in IMCD are considered to occur in IMCD1, simply because IMCD1 is dominant in population among IMCD subsegments. As target sites of AVP, IMCD subsegments are similar to OMCD.
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PMID:Effects of ANF on cGMP synthesis in inner medullary collecting duct subsegments of rats. 216 80

Regulation of urea transport by vasopressin in inner medullary collecting duct (IMCD) cells is thought to be important for the urinary concentrating mechanism. Isolated tubule perfusion studies suggest the existence of a saturable urea carrier. We have measured 14C-urea efflux in IMCD cells which were freshly isolated and grown in primary culture. Cells were isolated from rat papilla by collagenase digestion and hypotonic shock. In suspended cells, 14C-urea efflux (Jurea) from loaded cells was exponential with time constant 59 +/- 3 sec (SEM, n = 6, 23 degrees C). Jurea had an activation energy of 4.1 kcal/mole and was inhibited 42 +/- 7% by 0.25 mM phloretin and 30-40% by the high affinity urea analogues dimethylurea and phenylurea. Jurea was increased 40-60% by addition of vasopressin (10(-8) M) or 8-bromo-cAMP (1 mM); stimulated Jurea was inhibited 55 +/- 8% by the kinase A inhibitor H-8. Phorbol esters and epidermal growth factor did not alter Jurea. IMCD cells grown in primary culture were homogeneous in appearance with greater than fivefold stimulation of cAMP by vasopressin. The exponential time constant for urea efflux was 610 +/- 20 sec (n = 3). Jurea was not altered by vasopressin, cAMP or phloretin. Another function of in vivo IMCD cells, vasopressin-dependent formation of endosomes containing water channels, was absent in the cultured cells. These results demonstrate presence of a urea transporter on suspended IMCD cells which is activated by cAMP and inhibited by phloretin and urea analogues. The urea transporter and its regulation by cAMP, and cAMP-dependent apical membrane endocytosis, are lost after growth in primary culture.
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PMID:Urea transport in freshly isolated and cultured cells from rat inner medullary collecting duct. 217 46

The terminal part of the inner medullary collecting duct (terminal IMCD) is unique among collecting duct segments in part because its permeability to urea is regulated by vasopressin. The urea permeability can rise to extremely high levels (greater than 100 x 10(-5) cm/s) in response to vasopressin. Recent studies in isolated perfused IMCD segments have established that the rapid movement of urea across the tubule epithelium occurs via a specialized urea transporter, presumably an intrinsic membrane protein, present in both the apical and basolateral membranes. This urea transporter has properties similar to those of the urea transporters in mammalian erythrocytes and in toad urinary bladder, namely, inhibition by phloretin, inhibition by urea analogues, saturation kinetics in equilibrium-exchange experiments, and regulation by vasopressin. The urea transport pathway is distinct from and independent of the vasopressin-regulated water channel. The increase in transepithelial urea transport in response to vasopressin is mediated by adenosine 3',5'-cyclic monophosphate and is associated with an increase in the urea permeability of the apical membrane. However, little is known about the physical events associated with the activation or insertion of urea transporters in the apical membrane. Because of the importance of this transporter to the urinary concentrating mechanism, efforts toward understanding its molecular structure and the molecular basis of its regulation appear to be justified.
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PMID:The vasopressin-regulated urea transporter in renal inner medullary collecting duct. 220 74

The distal inner medullary collecting duct (IMCD) is critical in the urinary concentrating process, in part because it is the site of vasopressin (AVP)-regulated permeability to urea. The purpose of these experiments was to develop a cell culture model of the IMCD on permeable structure and to characterize the responsiveness to AVP. Rat IMCD cells were grown to confluence on collagen-coated Millipore filters glued onto plastic rings. To assess the time required to achieve confluence, the transepithelial resistance was measured periodically and was found to be stable after 2 weeks, at a maximal value of 595 +/- 22 omega cm2. In separate monolayers the effect of AVP on inulin and urea permeability was determined. While inulin permeability was unchanged after AVP, urea permeability increased from 6.0 +/- 0.4 to peak values of 16.0 +/- 3.8 (10 nM), 23.1 +/- 3.9 (1 microM) and 28.1 +/- 4.9 (10 microM) x 10(-6) cm s-1 (n = 24). In 10 other monolayers, after the addition of 1 mM 8-Br-cAMP, urea permeability increased from 5.1 +/- 0.3 to 8.1 +/- 1.6 x 10(-6) cm s-1 and, after 8-Br-cAMP + 3-isobutyl-1-methylxanthine, to 12.2 +/- 0.7 x 10(-6) cm s-1. We conclude that rat IMCD cells grown in culture exhibit the characteristics of a 'tight' epithelium. Inulin and urea permeability are not different in the absence of AVP, consistent with high resistance junctional complexes. Furthermore, IMCD cells retain the capacity for AVP-regulated urea permeability, a characteristic feature of this nephron segment in vivo.
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PMID:Vasopressin-enhanced urea transport by rat inner medullary collecting duct cells in culture. 224 45

The capacity of papillary cells to adapt to elevated osmotic concentrations is unusual among mammalian cells. This capacity was evaluated by using primary tissue culture. Viability and growth of cells in rat renal papillary tissue explants were assessed after culture in media adjusted with urea and sodium chloride to various osmotic concentrations between 300 and 1,500 mOsm/kg water. The survival of cells, including cells resembling those of the collecting ducts and the loop of Henle, was greatest in medium adjusted to 1,000 mOsm with equiosmolar amounts of the two solutes. At 1,500 mOsm only cuboidal tubular epithelium resembling collecting duct epithelial cells survived. In contrast, cells of cortical tissue survived and grew at 300 and 640 mOsm, but not at 1,000 mOsm or above. Epithelial monolayers appeared to proliferate from collecting ducts and spread over the surface of the explants as well as onto the glass surface in the culture dish. Epithelial growth of medullary tissue was most rapid at 300 mOsm and was slower at 700 and 1,000 mOsm. Monolayers did not form at 1,500 mOsm; however, epithelial overgrowth of explants did occur. Hydropenia in the donor animal did not significantly affect the viability or growth of cultured papillary tissue. Explants cultured for 5 days at 300 mOsm followed by a stepwise increase in medium osmolality to 1,100 or 1,500 mOsm and cultured for 3 more days showed low or no survival whereas explants cultured at 700 mOsm survived such increases. Explants cultured for 5 days at 1,500 mOsm survived and grew monolayers when lowered to 300 mOsm. Poor viability and no epithelial proliferation were observed in explants cultured in medium adjusted to 900 mOsm with either urea or sodium chloride alone, suggesting that a mixture of the two solutes in the extracellular space, as found in vivo, may be essential in achieving elevated osmolalities.
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PMID:Rat renal papillary tissue explants survive and produce epithelial monolayers in culture media made hyperosmotic with sodium chloride and urea. 228 Feb 48

The role of vasopressin in the kidney has classically been considered to result from its ability to increase water permeability in the collecting duct. Recent data, however, suggest that the hormone may also promote urinary concentration by increasing interstitial tonicity. The mechanisms whereby vasopressin could enhance interstitial tonicity include increasing urea permeability in the inner medullary collecting tubule, stimulation of solute reabsorption in the thick ascending limb of the loop of Henle, increasing the glomerular filtration rate of juxtamedullary nephrons, and decreasing vasa recta blood flow. We review experiments directed at assessing the role of vasopressin in these four processes. The multitude of effects of vasopressin appears to be well integrated and contributes to the tightly regulated urinary concentration mechanisms.
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PMID:Vasopressin and the concentrating mechanism. 243 73

Arginine vasopressin (AVP) increases the urea permeability of the rat terminal inner medullary collecting duct (IMCD) to levels much greater than can be explained by lipid-phase permeation or paracellular diffusion, suggesting the presence of an AVP-stimulated facilitated transport pathway. We tested whether inhibitors of facilitated urea transport in erythrocytes and toad bladder also inhibit urea transport in the isolated perfused IMCD. Apparent urea permeability (Purea) was determined by measuring the flux due to an imposed 5 mM concentration gradient. Phloretin (0.25 mM in lumen or bath) reversibly inhibited Purea. Phloretin, however, did not alter the osmotic water permeability. Urea analogues (200 mM) in the bath inhibited Purea (thiourea, 74% inhibition; methylurea 65%; acetamide 35%). Urea analogues in the lumen decreased Purea with the same order of potency. The inhibitory K1/2 for thiourea in the lumen was 27 +/- 2 mM and did not change with 10(-10) M AVP (28 +/- 3), despite a fourfold increase in Purea. We conclude the following. 1) Inhibitor actions on urea transport in the IMCD are similar to those in red blood cells and toad bladder, suggesting that the urea transporter could be a membrane protein similar to that in the other tissues. 2) Inhibition of Purea by phloretin without an effect on vasopressin-stimulated water permeability supports the view that the urea pathway is not the vasopressin-stimulated water channel. 3) The ability of AVP to increase Purea without an effect on the inhibitory K1/2 for thiourea indicates that AVP probably does not act by altering the binding affinity of individual transporters for urea.
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PMID:Inhibition of urea transport in inner medullary collecting duct by phloretin and urea analogues. 250 65

Urea production from arginine was studied in vitro in the kidney of normal rats in tubule suspensions of the four different renal zones (cortex, outer and inner stripe of outer medulla, and inner medulla), and in individual microdissected nephron segments. Tissue was incubated with L-[guanido-14C]-arginine to measure cellular arginase activity. Addition of urease to the incubate freed 14CO2 from the 14C-urea formed by arginase and released from the cells. CO2 was trapped in KOH and counted. These experiments revealed that significant amounts of urea are produced in the outer stripe and in the inner medulla. This intrarenal urea generation takes place mainly in the proximal straight tubule and in the collecting duct, with increasing activity in these two structures from superficial to deep regions of the kidney. Urea is known to play a critical role in the urinary concentrating process. The fact that some urea can be produced in the mammalian kidney, and that the two structures showing this capacity are straight portions of the renal tubular system descending along the corticopapillary axis suggest that this urea production might play a role in the formation and/or maintenance of the medullary urea concentration gradient.
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PMID:Production of urea from arginine in pars recta and collecting duct of the rat kidney. 251 52

Atrial natriuretic factor (ANF) is a peptide hormone that increases renal NaCl and water excretion. Several renal sites of ANF action have been identified, but general agreement has not been reached concerning the quantitative contribution of each action to the natriuresis and diuresis. Using a five-nephron central core model of NaCl, urea, KCl, and water transport in the rat kidney, we have quantitatively evaluated the hypothetical effects on whole kidney function of three experimentally observed ANF actions: 1) inhibition of active NaCl absorption in the collecting duct, 2) inhibition of osmotic water permeability in the collecting duct, and 3) increased NaCl and water delivery out of the proximal convoluted tubule simulating an increase in glomerular filtration rate. The simulations show that inhibition of collecting duct active NaCl absorption by greater than or equal to 50% can increase NaCl and water excretion to levels that match experimental values. In addition, the model predicted that the urinary sodium concentration will increase to greater than plasma levels as observed experimentally. Simulated decreases in collecting duct water permeability predicted an increase in water excretion with little change in NaCl excretion. Simulated 2.5-5% increases in glomerular filtration rate also increased simulated NaCl and water excretion rates to experimentally observed levels in response to ANF. However, this action was less effective than inhibition of collecting duct active NaCl absorption in increasing the urinary NaCl concentration. We conclude that a combination of several actions are likely to account for the overall renal effect of ANF.
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PMID:Renal actions of atrial natriuretic factor: a mathematical modeling study. 253 76


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