UNIPROT:P41181 - FACTA Search

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

Our previous characterization of equilibrium binding kinetics of atrial natriuretic peptide (ANP) to the surface of inner medullary collecting duct (IMCD) cells suggested the existence of a single class of high-affinity receptors, functionally coupled to increases in cellular guanosine 3',5'-cyclic monophosphate (cGMP). We have now sought to understand the mode of regulation of this signal transduction system by studying the particulate guanylate cyclase (PGC) enzyme from these cells. PGC activity with and without ANP in membranes, made by homogenization and high-speed centrifugation of suspensions of IMCD cells, was linear up to 5 min and was stimulated by ANP [143 +/- 21 (ANP) vs. 38 +/- 7 (control) pmol/mg protein, n = 3, P less than 0.02]. Vmax increased more than threefold with ANP [130 +/- 19 (ANP) vs. 35 +/- 4 (control) pmol.mg protein-1.min-1, n = 4, P less than 0.005] without significant change in the Km [0.68 +/- 0.17 (ANP) vs. 0.55 +/- 0.08 (control) mM] of the enzyme. Half-maximal stimulation of guanylate cyclase activity occurred at 5 x 10(-10) M ANP, a concentration consistent with our binding data, and with physiological effect. PGC required divalent cations for basal activity and for ANP-stimulated activity; Mg2+ and Mn2+ were most potent in this respect, and Ca2+ was without effect. Both basal and stimulated PGC activities were inhibited in response to changes in the NaCl, but not urea concentration of the assay system. We conclude that binding to the single 120-130 kDa ANP receptor in IMCD cells results in stimulation of PGC by increasing its Vmax and thereby elevating intracellular cGMP, the likely mediator of ANP action in these cells.
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PMID:Characteristics of ANP-sensitive guanylate cyclase in inner medullary collecting duct cells. 256 78

This chapter shows how the mammalian kidney is able to regulate the excretion of water independently from that of solutes. For this function, which derives from several evolutionary steps among vertebrates, it takes advantage of the diluting ability of the thick ascending limb to produce osmotic energy which is then used to concentrate solutes in the urine. This concentration is permitted by a highly sophisticated architecture of nephrons and vessels in the renal medulla, combined with special permeability characteristics of the different nephron segments and specific hormonal regulation. Two different types of loops of Henle and several well-insulated vascular compartments contribute to this process. The major nitrogenous waste product, urea, is concentrated by an indirect process involving a transfer of osmotic energy from the outer to the inner medulla. As known for several decades, concentrating function is primarily regulated by the effect of antidiuretic hormone (ADH) on water permeability of the collecting duct. However, as discovered more recently, it is also largely dependent upon the effect of the same hormone on urea permeability in the terminal collecting duct. In addition, recent investigations have revealed a much more complex hormonal regulation of the concentrating process than previously thought. ADH itself acts on many other structures in the kidney, and many other hormones and mediators, the secretion of which is not thought to be influenced by the water status, do affect urine concentration either directly or by their interaction with ADH. Rodents display a wide spectrum of morphological and functional renal adaptations improving water conservation. Their study has brought a better understanding of the significant steps and anatomical structures that contribute to the concentrating process. Finally, it is also apparent that the capacity to concentrate urine is influenced in individual animals of a given species by the availability of water, by specific feeding patterns, and by the protein content of the diet.
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PMID:The role of the kidney in the maintenance of water balance. 269 39

Several published models of the renal concentration mechanism have assumed a reflection coefficient for urea in the inner medullary collecting duct (IMCD) that is less than unity, implying direct coupling between water and urea transport. In the present study, we used isolated perfused terminal IMCD segments and mathematical modeling of IMCD transport to determine the validity of this assumption. Mathematical simulations of IMCD transport, using recently published data on urea and water permeability, revealed that the method previously used to measure the reflection coefficient for urea underestimates the true value. The modeling results allowed us to design two new experimental protocols to determine the reflection coefficient for urea. In the first protocol, we measured the ability of a transepithelial urea gradient to induce a water flux, correcting for the dissipation of the urea gradient by rapid passive urea permeation. In the second protocol, we directly measured the solvent drag of urea resulting from an osmotically induced water flux. Both protocols yielded values for the urea reflection coefficient that were not significantly different from unity (0.92 +/- 0.04 and 1.07 +/- 0.05, respectively). Thus we find no evidence for direct coupling between urea and water transport in the rat terminal IMCD.
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PMID:Independence of urea and water transport in rat inner medullary collecting duct. 270 34

In order to study the mechanisms involved in the regulation of renal inner medullary sorbitol content, collecting duct cells were isolated from rat inner medulla and the effect of extracellular osmolarity on sorbitol synthesis and sorbitol content was investigated. Cells isolated at 300 mosmol/l and incubated up to 24 h as primary cultures in 300 mosmol/l media or in media made 600 mosmol/l by the addition of 150 mM NaCl showed no difference in total synthesis. Intracellular sorbitol content was, however, 2.3-fold higher in the cells kept in the higher osmotic medium. Cells isolated at 600 mosmol/l released sorbitol about 8 times faster when transferred into hypoosmotic medium (300 mosmol/l) than when transferred into isoosmotic (600 mosmol/l) media. Cells exposed to hyperosmotic media (900 mosmol/l with NaCl) maintained a higher intracellular sorbitol content than cells incubated in isoosmotic media. Changes of intracellular sorbitol content could not be attributed entirely to cell lysis--as demonstrated by determination of cellular content of lactate and lactate dehydrogenase. The alteration in sorbitol membrane permeability was reversible and was only observed when poorly permeable solutes (such as NaCl and sucrose) were used for the experiments, changes in urea elicited no effect. It is proposed that rapid changes in membrane permeability to sorbitol play an important role in the adjustment of intracellular sorbitol concentration in inner medullary collecting duct cells to changes in extracellular osmolarity.
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PMID:Intracellular sorbitol content in isolated rat inner medullary collecting duct cells. Regulation by extracellular osmolarity. 275 72

A one-nephron model has been extended to include both short-looped and long-looped nephrons. Variables are volume flow, Na+, K+, Cl-, urea, hydrostatic pressure, and electric potential. The ratio of short-to-long-looped nephrons, one of the parameters of the model, is 5 to 1. With either rabbit or hamster permeability data from perfusion experiments, the model develops an osmolality of approximately 600 mosmol/l at the junction of inner and outer medulla but no osmolality gradient in the inner medulla. With the rabbit data, osmolalities in excess of 1,000 mosmol/l can be generated in the papilla with no active transport if urea permeabilities are less than 10(-5) cm/s; with the hamster data, electrolyte permeabilities must also be reduced. With these modified parameters, urea concentrations are less in the long loops than has been found on micropuncture. These can be increased to experimental levels by increasing the urea permeability and decreasing the hydraulic permeability of thin descending limbs in the inner half of the inner medulla, but to maintain loop osmolality at 1,000 mosmol/l it is necessary to postulate active NaCl transport in thin ascending limbs in the outer half of the inner medulla. This gives an alternative mode of concentration without active transport in the inner half of the inner medulla, in which electrolytes diffuse out of and urea diffuses into both limbs of Henle's loop and mix in the core with urea and water entering from the collecting duct. Concentration in either mode requires significant modification of perfusion data.
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PMID:Electrolyte, urea, and water transport in a two-nephron central core model of the renal medulla. 278 22

The inner medullary collecting duct (IMCD) has been proposed to be a site of atrial natriuretic factor (ANF) action. We carried out experiments in isolated perfused terminal IMCDs to determine whether ANF (rat ANF 1-28) affects either osmotic water permeability (Pf) or urea permeability. In the presence of a submaximally stimulating concentration of vasopressin (10(-11) M), ANF (100 nM) significantly reduced Pf by an average of 46%. Lower concentrations of ANF also significantly inhibited vasopressin-stimulated Pf by the following percentages: 0.01 nM ANF, 18%; 0.1 nM, 46%; 1 nM, 48%. Addition of exogenous cyclic GMP (0.1 mM) mimicked the effect of ANF, decreasing Pf by an average of 48%. ANF also inhibited cyclic AMP-stimulated Pf by an average of 31%. ANF did not affect urea permeability, nor did it alter vasopressin-stimulated cyclic AMP accumulation. We conclude that ANF at physiological concentrations causes a large inhibition of vasopressin-stimulated Pf in the rat terminal IMCD, and that cyclic GMP is the second messenger mediating the effect. ANF appears to act at a site distal to cyclic AMP generation in the chain of events linking vasopressin receptor binding to an increase in osmotic water permeability.
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PMID:Atrial natriuretic factor inhibits vasopressin-stimulated osmotic water permeability in rat inner medullary collecting duct. 284 55

The relationship between structure and function in the distal tubule and collecting duct has been studied with morphologic and physiologic techniques, including morphometric analysis, to identify functionally distinct cell populations. The distal tubule, including the thick ascending limb (TAL) and the distal convoluted tubule (DCT), is involved in active reabsorption of sodium chloride. It is characterized by extensive invaginations of the basolateral plasma membrane, numerous mitochondria, and high Na-K-ATPase activity, features characteristic for an epithelium involved in active transport. Between the distal tubule and the collecting duct is a transition region, the connecting segment or the connecting tubule (CNT), which exhibits species differences with respect to both structure and function. The collecting duct includes the cortical (CCD), the outer medullary (OMCD), and the inner medullary (IMCD) collecting ducts. Principal cells are present throughout the collecting duct, whereas intercalated cells are located mainly in the CCD and OMCD. Morphometric analysis combined with micropuncture and microperfusion studies has provided evidence that the CNT and principal cells are responsible for potassium secretion in the connecting segment and the CCD. The OMCD is a main site of hydrogen ion secretion, and morphometric studies have provided evidence that the intercalated cells in this segment secrete hydrogen ion at least in the rat. Two configurations of intercalated cells exist in the CCD--a type A and a type B. The A cells are similar in ultrastructure to the intercalated cells in the OMCD and are believed to be involved in hydrogen ion secretion. The function of the B cells remains to be established. The inner two-thirds of the IMCD corresponds to the papillary collecting duct, which has a high permeability to urea. The relationship between structure and function in the IMCD has not been studied in detail. This review emphasizes the role of morphometric analysis in establishing the relationship between structure and function in the distal nephron.
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PMID:Relationship between structure and function in distal tubule and collecting duct. 305 90

The physical properties and chemical composition of urine are highly variable and are determined in large measure by the quantity and the type of food consumed. The specific gravity is the ratio of the density to that of water, and it is dependent on the number and weight of solute particles and on the temperature of the sample. The weight of solute particles is constituted mainly of urea (73%), chloride (5.4%), sodium (5.1%), potassium (2.4%), phosphate (2.0%), uric acid (1.7%), and sulfate (1.3%). Nevertheless, urine osmolality depends only on the number of solute particles. The renal production of maximally concentrated urine and formation of dilute urine may be reduced to two basic elements: (1) generation and maintenance of a renal medullary solute concentration hypertonic to plasma and (2) a mechanism for osmotic equilibration between the inner medulla and the collecting duct fluid. The interaction of the renal medullary countercurrent system, circulating levels of antidiuretic hormone, and thirst regulates water metabolism. Renin, aldosterone, prostaglandins, and kinins also play a role. Clinical estimation of the concentrating and diluting capacity can be performed by relatively simple provocative tests. However, urinary specific gravity after taking no fluids for 12 h overnight should be 1.025 or more, so that the second urine in the morning is a useful sample for screening purposes. Many preservation procedures affect specific gravity measurements. The concentration of solids (or water) in urine can be measured by weighing, hydrometer, refractometry, surface tension, osmolality, a reagent strip, or oscillations of a capillary tube. These measurements are interrelated, not identical. Urinary density measurement is useful to assess the disorders of water balance and to discriminate between prerenal azotemia and acute tubular necrosis. The water balance regulates the serum sodium concentration, therefore disorders are revealed by hypo- and hypernatremia. The disturbances are due to renal and nonrenal diseases, mainly liver, cardiovascular, intestinal, endocrine, and iatrogenic. Fluid management is an important topic of intensive care medicine. Moreover, the usefulness of specific gravity measurement of urine lies in interpreting other findings of urinalysis, both chemical and microscopical.
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PMID:Relative density of urine: methods and clinical significance. 307 30

Using the in vitro microperfusion technique on isolated rat papillary collecting duct (PCD), we examined whether the glutaraldehyde-fixation method can be also applied to the mammalian collecting duct for preservation of the vasopressin-stimulated water and urea transport. Arginine vasopressin (AVP) at 10(-9) mol/l increased diffusional water permeability (Pdw) from 101.9 +/- 10.76 to 283.3 +/- 16.67 X 10(-7) cm2 s-1 (n = 8, P less than 0.01) and urea permeability (Purea) from 30.3 +/- 2.24 to 83.5 +/- 7.80 X 10(-7) cm2 s-1 (n = 8, P less than 0.01). Both parameters remained elevated after fixation with 0.1 mol/l glutaraldehyde even in the absence of AVP, with the values being 265.0 +/- 14.47 and 74.5 +/- 7.15 X 10(-7) cm2 s-1, respectively. Glutaraldehyde fixation did not affect the basal levels of Pdw or Purea. Phloretin at 2.5 X 10(-4) mol/l decreased glutaraldehyde-fixed AVP-stimulated Purea from 79.0 +/- 7.96 to 29.7 +/- 3.66 X 10(-7) cm2 s-1 (n = 4, P less than 0.01) and from 73.2 +/- 7.05 to 38.7 +/- 3.53 X 10(-7) cm2 s-1 (n = 4, P less than 0.01) when the drug was added to the lumen or to the bath, respectively. Phloretin also decreased glutaraldehyde-fixed non-stimulated Purea by 25-40%. However, this drug did not affect glutaraldehyde-fixed Pdw. These findings indicate that the glutaraldehyde fixation method can be applied to mammalian collecting tubules for studying vasopressin stimulated Pdw and Purea. Purea fixed by glutaraldehyde is functionally flexible and may be distinct from the water pathway.
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PMID:Effects of glutaraldehyde fixation on renal tubular function. I. Preservation of vasopressin-stimulated water and urea pathways in rat papillary collecting duct. 311 Jul 36

Osmotic diuresis occurs, if nonreabsorbed solutes such as mannitol impair the reabsorption of water. The reduced reabsorption of volume affects in turn the reabsorption and excretion of solutes. Thus, mannitol leads to modest impairment of proximal tubular reabsorption not only of water, but as well of electrolytes (Na, Cl, K, Pi, Ca, but not Mg), urea, and uric acid. Infusion of hypertonic mannitol increases renal blood flow and the glomerular filtration rate of superficial nephrons. The increased perfusion of medulla leads to wash out of medullary hypertonicity. The decline of medullary osmolarity leads to a marked impairment of water reabsorption in descending limbs and possibly to moderate impairment of NaCl, Ca, and Mg reabsorption in the ascending limbs of Henle's loop. In the collecting duct, inhibition is marked of water and urea reabsorption and modest of NaCl reabsorption. A number of open questions remain, such as the mechanisms underlying decrease of renal vascular resistance, increased proximal tubular reabsorption of magnesium, or impaired NaCl reabsorption in thick ascending limbs.
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PMID:Osmotic diuresis. 313 29

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