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)

Kallikrein excreted with the urine appears to be formed in the kidney. The kallikrein-kinin system in the kidney is localized in the distal nephron from the juxtaglomerular apparatus to the collecting duct. It has been shown that intrarenal infusion of kinins produces an increase in renal blood flow as well as diuresis and natriuresis. Part of the effect of kinins appears to be mediated by the release of prostaglandins. However, the precise role of the renal kallikrein-kinin system in sodium and volume homeostasis and in blood pressure regulation still remains to be determined. Mineralocorticoids as well as the diuretics furosemide, bumetanide and bendroflumethiazide increase, spironolactone decreases kallikrein excretion. Urinary kallikrein has been shown to increase acid-as well as cryoactivation of prorenin in vitro. It is unclear as yet, however, whether the renal kallikrein-kinin system takes part in converting inactive prorenin into active renin in vivo. There are reports on subnormal, normal as well as increased kallikrein excretion in spontaneously hypertensive rats. In rats susceptible to the hypertensive effect of salt a substantially decreased excretion of kallikrein has been observed. Kallikrein excretion has been described to be increased in primary aldosteronism and to be reduced in a proportion of patients with established essential hypertension. In patients with labile hypertension, however, kallikrein excretion appears to be normal suggesting that decreased urinary kallikrein in essential hypertension is a consequence rather than a cause of hypertension. The renal kallikrein-kinin system does not appear to play a primary role in the pathogenesis of hypertension.
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PMID:[Renal kallikrein-kinin system and control of blood pressure (author's transl)]. 39 77

Diuretics act primarily by blocking reabsorption of sodium at four major sites in the nephron. Clinically useful agents that block sodium reabsorption effectively in the proximal tubule are lacking. Furosemide (Lasix), ethacrynic acid (Edecrin), and possibly organomercurial agents are effective in the ascending limb of Henle's loop. Thiazides are the major agents acting in the early distal tubule. In the late distal tubule and collecting duct, spironolactone (Aldactone) and triamterene (Dyrenium) are useful, especially in combination with diuretics which act more proximally. In treating edematous states, initial therapy with thiazides is effective in most patients who do not exhibit moderate or severe renal insufficiency, severe hyperaldosteronism with excessive distal reabsorption of sodium in exchange for potassium, or excessive sodium reabsorption in the proximal tubule or ascending limb. Nonedematous states in which diuretic therapy is useful include hypertension, hypercalcemia, hypercalciuria, diabetes insipidus, and acute renal failure.
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PMID:Diuretic agents. Mechanisms of action and clinical uses. 126 95

To investigate the sites of action of aldosterone (Aldo) and chronic potassium loading (high K) and to determine whether dietary K can modulate collecting duct structure independent of Aldo, a morphometric study of the structure of the initial collecting tubule (ICT), the cortical collecting tubule (CCT), the medullary collecting duct in the outer stripe (MCDOS) and the inner stripe (MCDIS), and the papillary collecting duct (PCD) was carried out in a rat model in which plasma levels of Aldo were clamped at basal or physiologically elevated levels and high K could be induced without concomitant hyperaldosteronism. Elevated levels of Aldo increased cell area (Ac) and basolateral membrane surface (BLM) from control values in the ICT, CCT, and MCDOS but not in the MCDIS or PCD. High K with normal physiological levels of Aldo increased BLM in the ICT and CCT without a concomitant change in AC. No response was seen in MCDOS, MCDIS, or PCD. It is concluded that Aldo can modulate principal cell structure in the collecting duct system in segments extending from the ICT through the MCDOS in the rat and that high K independent of Aldo can influence collecting duct structure only in the ICT and CCT.
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PMID:Response of collecting tubule cells to aldosterone and potassium loading. 360 52

Studies were performed on the initial collecting tubule of the rat to determine whether potassium adaptation in this nephron segment is aldosterone-dependent. Previous studies demonstrated that chronic potassium loading, in animals with intact adrenal glands, caused an increase in transepithelial potential difference in late distal convolution, an increase in surface density of the basolateral cell membrane, SVBLM, of principal cells in the initial collecting duct, and a rise in plasma aldosterone levels. The present study shows that epithelial changes that characterize dietary potassium loading are not dependent on hyperaldosteronism, since potential difference (-47 +/- 1 vs. 40 +/- 3 mV, lumen negative) and SVBLM (2.91 +/- 0.11 vs. 2.53 +/- 0.09 micron2/micron3) increased significantly (P less than 0.05) in the late distal convolution of adrenalectomized, hormone-replaced animals in which plasma aldosterone levels were maintained at basal values of approximately 5 ng/dl. In addition, these experiments suggest that the initial collecting tubule is sensitive to the action of aldosterone, at physiological plasma levels, since chronic hyperaldosteronism, in the absence of potassium loading, increased SVBLM in initial collecting tubule cells. In contrast to other mineralocorticoid-sensitive tissues, however, neither the acute or chronic administration of aldosterone caused an increase in potential difference in late distal convolution. These results suggest that the mechanism by which aldosterone stimulates electrolyte movement is not identical in all target tissues.
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PMID:Role of aldosterone in the mechanism of potassium adaptation in the initial collecting tubule. 609 57

In this review, the distal nephron is considered to be that portion of the renal tubule commencing with the thick ascending limb of the loop of Henle and ending with the papillary collecting duct. The collecting duct, including its subdivisions in the cortex and medulla, originates from a different embryologic anlage than more proximal nephron segments, which may explain its morphologic and functional dissimilarities from the thick ascending limb and the distal convoluted tubule. This review summarizes selected aspects of the physiology of the distal nephron, with particular emphasis on the physiology of distal nephron transport of sodium, potassium, chloride and hydrogen ion. The pathophysiologic features of the following disorders of distal nephron function are reviewed: (1) pseudohypoaldosteronism, a heterogenous group of disorders in which the signs and symptoms are suggestive of aldosterone deficiency, but in which aldosterone levels are supernormal and administration of exogenous mineralocorticoid is not ameliorative; (2) pseudohyperaldosteronism (Liddle syndrome), a familial disorder in which the clinical manifestations closely resemble those resulting from an aldosterone-producing adenoma of the adrenal gland (primary aldosteronism), but in which the measured rate of aldosterone secretion and excretion is greatly subnormal; (3) Bartter syndrome and related syndromes of renal potassium wasting; (4) type 1 renal tubular acidosis (classic, distal); (5) type 4 renal tubular acidosis (hyperkalemic). Reference citations are generally to articles reporting recent advances in these areas and to review articles that contain comprehensive bibliographies.
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PMID:Disorders of distal nephron function. 627 92

1. Tsukuba hypertensive mice (THM) carry both human renin and angiotensinogen genes, and develop hypertension. The animal has high levels of renin activity and angiotensin II concentration in the plasma. 2. Urinary excretion in THM was greater than in the control animal, non-transgenic C57BL/6j. THM showed a greater amount of daily water intake. The osmolality of 24 h urine was lower than that of the control animal. 3. When water was deprived for 12 h and then loaded with 0.25 mL/10 g bodyweight, the osmolality of urine at the first 0-3 h period was the same in THM and control, but significantly lower in THM at the following 3-6 h period, indicating that the urine concentrating activity is insufficient in THM compared with the control animal. 4. Urinary excretion of vasopressin was significantly higher in THM. Plasma aldosterone concentration and urinary excretion of aldosterone were also higher in THM. Plasma potassium level was significantly low. 5. The mechanism underlying the pathophysiology of polyuria is not totally explained; however, hypokalaemia, which was probably the result of hyperaldosteronism, may be at least partially involved, since hypokalaemia is considered to be a factor hampering the action of vasopressin for concentration of urine at the site of the collecting duct of the kidney.
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PMID:Development of polyuria in Tsukuba hypertensive mice carrying human renin and angiotensinogen genes. 907 20

Low-renin hypertension is common and usually implies increased retention of sodium (Na(+)). In every case of known etiology, there is a mineralocorticoid-induced increase in number of epithelial Na(+) channels (ENaCs) in the collecting duct of the kidney, leading to a state of "hyperENaCactivity." In primary aldosteronism, a result of either an adrenal adenoma or bilateral adrenal hyperplasia, aldosterone itself mediates the increase in ENaC function. A severe form of low-renin hypertension in which a molecular mutation in ENaC prevents removal of the channel from the cell surface, known as Liddle's syndrome, results in increased net ENaC activity but, in this case, independently of an increase in aldosterone. Glucocorticoid remedial aldosteronism, an autosomal dominant form of primary aldosteronism, results from a "new" or chimeric gene for aldosterone synthase. Adrenocorticotropic hormone stimulates its expression as well as secretion of aldosterone. Apparent mineralocorticoid excess results from a molecular mutation that allows cortisol to bind to the mineralocorticoid receptor. Both glucocorticoid remedial aldosteronism and apparent mineralocorticoid excess result in an increase in the number of ENaCs. The question remains whether low-renin essential hypertension is related to an increase in ENaC activity. Low-renin hypertension is most common in black patients, who tend to have lower levels of aldosterone as well as renin, which are features that resemble those found in Liddle's syndrome. Preliminary findings suggest that black patients with low-renin hypertension who are resistant to standard antihypertensive therapy respond favorably to the addition of spironolactone, a mineralocorticoid receptor antagonist that reduces ENaC activity.
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PMID:Low-renin hypertension: more common than we think? 1117 96

Prostasin is a serine protease present in mammalian urine that increases the activity of the epithelial sodium channel (ENaC) when the two are coexpressed in Xenopus oocytes. To determine if aldosterone, one of the principal regulators of urinary Na reabsorption by the distal nephron, affects prostasin expression, we examined prostasin mRNA and protein in a cultured mouse cortical collecting duct cell line (M-1), whole rats, and patients with primary aldosteronism. Aldosterone treatment of M-1 cells substantially increased prostasin expression and stimulated (22)Na uptake. Urinary excretion of prostasin in rats that were infused with aldosterone likewise increased by approximately 4-fold when compared with the vehicle-infused rats. Finally, urinary excretion of prostasin in patients with primary aldosteronism was substantially increased when compared with normal patients. Adrenalectomy reduced urinary prostasin excretion to control levels, whereas urinary prostasin levels were not altered in patients undergoing surgery for other reasons. In patients with primary aldosteronism, reduction in the urinary excretion of prostasin correlated with the increase in the urinary Na/K ratio. These findings, together with our previous report that prostasin activates the amiloride-sensitive Na currents through ENaC, demonstrate that prostasin regulates Na balance in vivo by virtue of its heightened expression in the presence of aldosterone.
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PMID:Regulation of prostasin by aldosterone in the kidney. 1182

Recent studies indicate that pendrin, an apical Cl-/HCO3- exchanger, mediates chloride reabsorption in the connecting tubule and the cortical collecting duct and therefore is involved in extracellular fluid volume regulation. The purpose of this study was to test whether pendrin is regulated in vivo primarily by factors that are associated with changes in renal chloride transport, by aldosterone, or by the combination of both determinants. For achievement of this goal, pendrin protein abundance was studied by semiquantitative immunoblotting in different mouse models with altered aldosterone secretion or tubular chloride transport, including NaCl loading, hydrochlorothiazide administration, NaCl co-transporter knockout mice, and mice with Liddle's mutation. The parallel regulation of the aldosterone-regulated epithelial sodium channel (ENaC) was examined as a control for biologic effects of aldosterone. Major changes in pendrin protein expression were found in experimental models that are associated with altered renal chloride transport, whereas no significant changes were detected in pendrin protein abundance in models with altered aldosterone secretion. Moreover, in response to hydrochlorothiazide administration, pendrin was downregulated despite a marked secondary hyperaldosteronism. In contrast, alpha-ENaC was markedly upregulated, and the molecular weight of a large fraction of gamma-ENaC subunits was shifted from 85 to 70 kD, consistent with previous results from rat models with elevated plasma aldosterone levels. These results suggest that factors that are associated with changes in distal chloride delivery govern pendrin expression in the connecting tubule and cortical collecting duct.
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PMID:Pendrin regulation in mouse kidney primarily is chloride-dependent. 1682 34

Among the causes of secondary hypertension are a group of disorders with a Mendelian inheritance pattern. Recent advances in molecular biology have unveiled the pathogenesis of hypertension in many of these conditions. Remarkably, the mechanism in every case has proved to be upregulation of sodium (Na) reabsorption in the distal nephron, with accompanying expansion of extracellular volume. In one group, the mutations involve the Na-transport machinery in distal tubule cells themselves: the distal convoluted tubule (DCT) cell and the principal cell of the collecting duct. Examples include Liddle's syndrome, with an activating mutation of epithelial Na channel (ENaC); two types of Gordon's syndrome, with mutations in two regulatory kinases [with no lysine (K) serine/threonine protein kinases (WNK)1 or WNK4]; and apparent mineralocorticoid excess (AME), with an inactivating mutation in the glucocorticoid-metabolizing 11beta-hydroxysteroid dehydrogenase type 2 enzyme (11HD2). In another group, abnormal adrenal steroid production leads to inappropriate stimulation of the mineralocorticoid receptor (MR) in the distal nephron. The pathophysiology may involve inappropriate production of aldosterone [in glucocorticoid-remediable aldosteronism (GRA) and familial hyperaldosteronism type II (FH II)], of cortisol (in familial glucocorticoid resistance), or of other steroid metabolites (in congenital adrenal hyperplasia and GRA). In contrast to earlier beliefs, hypertension in many of the inherited disorders may be mild, and electrolyte and acid-base abnormalities are often not present. Monogenic hypertension should therefore enter the differential diagnosis of any child or adolescent with hypertension. Plasma renin activity (PRA) is the appropriate screening tool for all types of inherited hypertension.
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PMID:Heritable forms of hypertension. 1764 25


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