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)

Utilization of classical clearance methodology for the determination of diuretic mechanism and site of action is based on four kinds of observations: (1) the effects of diuretic agents on the concentrating and diluting mechanism; (2) an analysis of the pattern of anionic excretion produced by the drug; (3) determination of the action of the agent on acid excretion and on acid-base status; (4) an evaluation of the effects of the diuretic on potassium excretion. Agents (such as acetazolamide) that act in the proximal convoluted tubule cause an enhancement of solute-free water generation (CH2O), induce a phosphaturia and an increase in bicarbonate excretion, alkalinize the urine, and cause a kaliuresis. Those agents which inhibit sodium chloride transport in the loop of Henle (for example, furosemide and ethacrynic acid) reduce both CH2O and the abstraction of tubular water from the collecting duct (TCH2O). They are the most potent natriuretic agents currently available, causing increments in the excretion of sodium in the urine of 15 to 25 per cent of filtered load. Those drugs which act in the early portion of the distal convolution (the thiazides, metolazone) reduce CH2O modestly or not at all and have no effect on TCH2O. They are capable of increasing urinary sodium by 5 to 8 per cent of the filtered load. The special-purpose agents such as triamterene and spironolactone are only mildly effective as natriuretic agents. While they augment fractional sodium excretion by only 2 to 3 per cent, they are useful because of their capacity to reduce urinary potassium excretion, either by a direct renal tubular effect (triamterene) or by competitive inhibition of aldosterone (spironolactone).
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PMID:Sites and mechanisms of action of diuretics in the kidney. 733 66

The effect of volume expansion on inner medullary collecting duct (IMCD) sodium transport remains controversial. Studies employing micropuncture of the IMCD base and tip were interpreted to demonstrate enhanced sodium and chloride reabsorption. Data obtained by microcatheterization evaluating only sodium transport revealed either no reabsorption or net addition. We have examined both sodium and chloride transport by microcatheterization. Volume expansion was comparable to the micropuncture studies: 0.9% saline equal to 10% body wt and then matched to urine flow. The fraction of filtered fluid, sodium, and chloride was analyzed as a function of IMCD length. In eight hydropenic rats 60% of the fluid, 71% of the sodium, and 48% of the chloride delivered to the IMCD was reabsorbed. In six volume-expanded rats no significant net reabsorption of fluid, sodium, or chloride was found. Accordingly, in contrast to the micropuncture results, we have demonstrated that net sodium chloride and fluid reabsorption are absent during volume expansion. We conclude that during volume expansion, fluid, sodium, and chloride excretion increase, in part, because of a reduction in net reabsorption along the IMCD. The degree of volume expansion does not account for the discrepancy between the two techniques.
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PMID:Sodium and chloride transport along the inner medullary collecting duct: effect of saline expansion. 738 29

A histophysiological study was made of the kidney of Amphipnous cuchia subjected to different osmotic conditions (distilled water, 50% and 15% sodium chloride solution). These fish possess typical glomerular kidneys having nephrons composed of a glomerular body, neck segment, proximal convoluted segment (I & II), distal segment, and collecting duct system. When subjected to a hypotonic medium (distilled water) the fish show marked expansion in glomeruli resulting in 'glomerulitis'. A marked shrinkage in glomerular body tissue is found after 50% salt solution treatment and the fish die within one hour of immersion. Many pathological changes occur in the renal capsule and renal segment when the fish are treated with 15% salt solution. The glomerular bodies show shrinkage, degeneration and cyst formation. The glomerular shrinkage is probably due to constriction of arterioles which affects the filtration rate and thus protects against loss of water. Formation of cysts could be a protective device to save the glomeruli from degeneration. The renal tubules show hypertrophy, vacuolization, nuclear degeneration and cyst formation.
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PMID:Structural changes in the kidney of freshwater mud eel Amphipnous cuchia (Ham.) subjected to different osmotic conditions. 744 47

1. Chronic reduction of salt intake can reduce the natriuretic effect of exogenously administered atrial natriuretic factor. The purpose of this study was to elucidate the intrarenal site(s) of such atrial natriuretic factor resistance. Renal clearance and collecting duct microcatheterization experiments were made before and during infusion of atrial natriuretic factor in three groups of rats: group 1 consisted of rats fed a high salt diet (8% NaCl) for 1 week before the experiment; group II were fed a low salt diet (< 0.008%); group III received the same low salt diet, but were acutely replenished with salt at the time of experiment. 2. Baseline sodium chloride excretion was 6480 +/- 810 nmol min-1 g-1 kidney weight in group 1 compared to 99 +/- 16 in group 1. Fractional reabsorptions in the medullary collecting duct were 37 +/- 6% and 95 +/- 2% of delivered load, respectively (P < 0.05). The fractions of filtered sodium remaining at the beginning of the medullary duct were 6.6 +/- 1.0% of filtered load in group 1 and 2.7 +/- 0.7% in group II (P < 0.05), indicating increased tubular reabsorption in group II, not only in the medullary duct, but also in upstream nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary salt extremes and renal function in rats: effect of atrial natriuretic factor. 787 40

Diuretics may be classified according to their chemical structure, their mechanism and site of action within the nephron, and their diuretic potency. Those agents with primary action in the proximal nephron include the carbonic anhydrase inhibitors, e.g. acetazolamide, a sulfonamide derivative. Other drugs containing the sulfonamido grouping, e.g. furosemide, chlorothiazide and metolazone, also have secondary effects on the proximal nephron. Those drugs which have their major pharmacologic activity within the ascending limb of the loop of Henle, inhibiting the sodium/potassium/2 chloride electroneutral transport system, include the sulfonamide agents furosemide, bumetanide, piretanide and torasemide, and the phenoxyacetic acid derivative, ethacrynic acid. In the early portion of the distal convoluted tubule, sodium chloride reabsorption is impaired by the thiazide group, indapamide and metolazone, as their primary site of action. In the late reaches of the distal convolution and in the collecting duct, agents that inhibit the exchange of sodium for that of hydrogen and potassium have their major sites of activity. These agents, spironolactone, amiloride and triamterene, differ not only chemically but in their mechanisms of action. Diuretics may also be grouped according to potency. The loop of Henle agents are the most powerful, causing the excretion of 20-25% of filtered sodium load. The thiazide group and metolazone are moderately potent, resulting in the excretion of 5-8% of filtered sodium, and the 'potassium-sparing' drugs are only mildly potent, causing the excretion of only 2-3% of filtered sodium.
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PMID:Pharmacological classification and renal actions of diuretics. 795 44

A selective antagonist for the cGMP-linked ANF receptor was used to assess inhibition of cardiovascular and renal actions of atrial natriuretic factor (ANF). Two groups of anesthetized rats were injected with antagonist or vehicle, respectively, prior to an infusion of ANF. A third group received neither antagonist injection nor ANF infusion and served as a time control. Compared to ANF infusion alone, prior antagonist administration was associated with significant reduction of both the hypotension and hemoconcentration following peptide infusion, although significant residual effects were still present. Glomerular filtration rates during ANF infusion were significantly lower in the antagonist group. The increases in urinary salt and water excretion were also partially blocked by the antagonist. Microcatheterization studies showed significant partial reversal of ANF-induced inhibition of sodium chloride and water reabsorption in the medullary collecting duct. We conclude that the antagonist is an effective specific blocker of the cardiovascular, renal hemodynamic, and tubular effects of ANF, providing a useful new tool to elucidate the regulatory roles of this peptide hormone system.
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PMID:Cardiovascular and renal functional effects of an antagonist of the guanylyl cyclase-linked ANF receptor. 814 Feb 74

In vitro studies on single microdissected segments have been extensively used during the 20 past years to localize V1 and V2 vasopressin receptors within the mammalian kidney, and define their role in the control of water balance. Based on vasopressin-dependent adenylate cyclase activity measurements and quantitative RT-PCR studies, it is now clear that V2 receptors are present along the whole collecting duct from cortex to papilla, and, in most species, in the ascending limb of Henle's loop (thick and thin limb); occasionally in the distal tubule but not in the other segments. The stimulation by cyclic AMP of sodium chloride reabsorption in the thick ascending limb, and of urea reabsorption in the papillary collecting duct indicates that vasopressin--in addition to its well known hydroosmotic effect--also participates in the building up of the corticopapillary gradient of osmotic pressure. As regards the V1a receptor, binding studies as well as quantitative RT-PCR, and measurements of free cytosolic calcium concentration allow us to draw the following conclusions. In the rat, the V1a receptor is absent from the glomerulus, the proximal tubule (convoluted and straight portions), the tick ascending limb of Henle's loop and the terminal portion of the papillary collecting duct. It is present in the thin ascending limb and the cortical and outer medullary portions of the collecting duct. Its presence in the thin descending limb has not, up to now, been explored. By contrast with previous data in the rabbit, the V1a receptor does not alter vasopressin-dependent sodium and water reabsorption in the rat cortical collecting duct. Further studies will be necessary to determine its functional role in that segment, as well as in the thin ascending limb. Finally, vasopressin V2 agonists have been shown to induce intracellular calcium release in the papillary collecting duct, a segment devoid of V1a receptors. This effect--which cannot be ascribed to a cross-reaction with oxytocic receptors--indicates either an unusual coupling of the V2 receptor to phospholipase C or, else, the presence of a new vasopressin receptor.
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PMID:[Functional expression of vasopressin receptors V1a and V2 along the mammalian nephron]. 859 Feb 15

The vasopressin-sensitive water channel (aquaporin 2; AQP-2) mediates water transport across the apical plasma membrane of the renal collecting ducts and is excreted in human urine. This study presents the hypothesis that measurements of the AQP-2 excretion rate might be used as a marker of collecting-duct responsiveness to vasopressin, and therefore could be useful in the clinical evaluation of various water-balance disorders. This study presents information about the development of an antibody to human AQP-2, and measures the urinary excretion of AQP-2 by quantitative Western analysis. A standard curve of band densities was generated by using known quantities of the modified immunizing peptide to derive the amount of AQP-2 contained in aliquots of urine. AQP-2 urinary excretion changed with short-term alterations in hydration status produced either by water loading (76% decrease, P < 0.01) or by 3% sodium chloride (760% increase, P < 0.01). Steady-state 24-h urinary excretion of AQP-2 was 43 +/- 10 nmol/24 h (or 28.5 +/- 6.9 pmol/mg creatinine), and 20 +/- 6 nmol/24 h (or 18.3 +/- 7.9 pmol/mg creatinine) in men and women, respectively. Therefore, urinary AQP-2 excretion can be quantified by using Western analysis, and may serve as a marker of collecting-duct responsiveness to vasopressin in different physiologic settings.
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PMID:Urinary excretion of aquaporin-2 in humans: a potential marker of collecting duct responsiveness to vasopressin. 870 5

While in vivo data suggests that diuretics such as furosemide and hydrochlorothiazide alter inner medulla collecting duct (IMCD) cell electrolyte transport, this has not been confirmed by in vivo studies nor have the mechanisms been evaluated. This study evaluated the direct effect of these diuretics as well as amiloride on sodium and chloride unidirectional permeability in the isolated perfused rat IMCD. In the absence of diuretics, the permeability of sodium was lower than that of chloride (0.63 +/- 0.05 compared with 0.83 +/- 0.08 micrometer/s), although both were relatively impermeable when compared to water. Furosemide (10(-4)) and hydrochlorothiazide (10(-3)) both increased the diffusional permeability of chloride by approximately 30% (0.80 +/- 0.06 to 1.04 +/- 0.09 micrometer/s, p < 0.01, and 0.74 +/- 0.09 to 0.98 +/- 0.10 micrometer/s, p < 0.02, respectively). However, sodium permeability was unaltered. Inhibition of Na+, K+-ATPase by ouabain or cooling (4 degrees C) inhibited basal sodium but not chloride permeability while a maximal antidiuretic AVP concentration did not alter sodium or chloride permeability. However, increasing the lumen and bath sodium chloride concentration from 150 to 300 and 600 mM significantly increased both sodium and particularly chloride conductance. In contrast, amiloride (10(-4)) significantly reduced both sodium and chloride permeability. These studies support a direct effect of furosemide and hydrochlorothiazide on the IMCD and suggest that their in vivo effect is primarily mediated by facilitating the passive movement of chloride into the lumen via a favourable electrochemical gradient. These results also demonstrate that amiloride inhibits both sodium and chloride unidirectional permeability by mechanisms separate to that of the sulphonamide-related diuretics.
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PMID:Effect of diuretics on sodium and chloride permeability in the rat papillary collecting duct. 976 78

Renal cyclooxygenase-1 and cyclooxygenase-2 actively metabolize arachidonate to metabolism five primary prostanoids: prostaglandin E2, prostaglandin F2a, prostaglandin I2, thromboxane A2, and prostaglandin D2. These lipid mediators interact with a family of distinct G-protein-coupled prostanoid receptors designated EP, FP, IP, TP, and DP, respectively, which exert important regulatory effects on renal function. The intrarenal distribution of these prostanoid receptors has been mapped and the consequences their activation are being characterized. The FP, TP, and EP1 receptors preferentially couple to increased cell Ca2+. EP2, EP4, DP, and IP receptors stimulate cyclic adenosine monophosphate, whereas the EP3 receptor preferentially couples to Gi, inhibiting cyclic adenosine monophosphate generation. EP1 and EP3 messenger RNA expression predominate in the collecting duct and thick limb, respectively, where their stimulation reduces sodium chloride and water absorption, promoting natriuresis and diuresis. Interestingly, only a mild change in renal water handling is seen in the EP3 receptor knockout mouse. Although only low levels EP2 receptor messenger RNA are detected in kidney and its precise intrarenal localization is uncertain, mice with targeted disruption of the EP2 receptor display salt-sensitive hypertension, suggesting it also plays an important role in salt excretion. In contrast, EP4 messenger RNA is readily detected in the glomerulus where it may contribute to the regulation of renin release and decrease glomerular resistance. TP receptors are also highly expressed in the glomerulus, where they may increase glomerular vascular resistance. The IP receptor messenger RNA is most highly expressed in the afferent arteriole and it may also modulate renal arterial resistance and renin release. At present there is little evidence for DP receptor expression in the kidney. Together these receptors act as physiologic buffers that protect the kidney from excessive functional changes during periods of physiologic stress. Loss of the combined effects of these receptors contributes to the side effects seen in the setting of nonsteroidal anti-inflammatory drug administration, whereas selective antagonists for these receptors may provide new therapeutic approaches in disease.
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PMID:Prostaglandin receptors: their role in regulating renal function. 1065 21


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