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)

This review updates our current knowledge on the regulation of Na+/H+ exchanger, Na+,K+,Cl- cotransporter, Na+,Pi cotransporter, and Na+,K+ pump in isolated epithelial cells from mammalian kidney by protein kinase C (PKC). In cells derived from different tubule segments, an activator of PKC, 4beta-phorbol 12-myristate 13-acetate (PMA), inhibits apical Na+/H+ exchanger (NHE3), Na+,Pi cotransport, and basolateral Na+,K+ cotransport (NKCCl) and augments Na+,K+ pump. In PMA-treated proximal tubules, activation of Na+,K+ pump probably plays a major role in increased reabsorption of salt and osmotically obliged water. In Madin-Darby canine kidney (MDCK) cells, which are highly abundant with intercalated cells from the collecting duct, PMA completely blocks Na+,K+,Cl- cotransport and decreases the activity of Na+,Pi cotransport by 30-40%. In these cells, agonists of P2 purinoceptors inhibit Na+,K+,Cl- and Na+,Pi cotransport by 50-70% via a PKC-independent pathway. In contrast with MDCK cells, in epithelial cells derived from proximal and distal tubules of the rabbit kidney, Na+,K+,Cl- cotransport is inhibited by PMA but is insensitive to P2 receptor activation. In proximal tubules, PKC-induced inhibition of NHE3 and Na+,Pi cotransporter can be triggered by parathyroid hormone. Both PKC and cAMP signaling contribute to dopaminergic inhibition of NHE3 and Na+,K+ pump. The receptors triggering PKC-mediated activation of Na+,K+ pump remain unknown. Recent data suggest that the PKC signaling system is involved in abnormalities of dopaminergic regulation of renal ion transport in hypertension and in the development of diabetic complications. The physiological and pathophysiological implications of PKC-independent regulation of renal ion transporters by P2 purinoceptors has not yet been examined.
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PMID:Na+,K+ pump and Na+-coupled ion carriers in isolated mammalian kidney epithelial cells: regulation by protein kinase C. 1053 80

Atrial natriuretic peptide (ANP) is thought to play a role in renal regulation of salt balance by reducing tubular reabsorption of sodium and chloride. Therefore, in the chronic absence of this hormone, a defect of salt excretion should be evident. We used an ANP gene deletion model to test this premise. F2 homozygous mutant mice (-/-) and their wild-type littermates (+/+) were fed an 8% NaCl diet prior to an acute infusion of isotonic saline. Arterial blood pressures, renal excretions of salt and water, as well as collecting duct transport of fluid and electrolytes were measured. Pressures were significantly higher in -/- compared with +/+ mice (139 +/- 4 vs. 101 +/- 2 mmHg; 1 mmHg = 133.3 Pa). There was no difference in glomerular filtration rate (-/- = 0.84 +/- 0.06; +/+ = 0.81 +/- 0.04 mL x min(-1) x g(-1) kidney weight). In the collecting duct, sodium and chloride reabsorptions were significantly higher in the -/- group than in the +/+ group. As a result, natriuresis and chloruresis were relatively reduced (U(Na)V: -/- = 8.6 +/- 1.1; +/+ = 14.0 +/- 1.1; U(Cl)V: -/- = 10.1 +/- 1.4; +/+ = 16.0 +/- 1.1 micromol x min(-1) x g(-1) kidney weight). We conclude that the absence of endogenous ANP activity in mice on a high-salt diet subjected to acute saline infusion causes inappropriately high reabsorption of sodium and chloride in the medullary collecting duct, resulting in a relative defect in renal excretory capacity for salt.
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PMID:Effect of saline infusion on kidney and collecting duct function in atrial natriuretic peptide (ANP) gene "knockout" mice. 1053 32

In addition to its hemodynamic effects, nitric oxide (NO) may play a role in the renal tubular handling of sodium. Experiments were conducted to determine possible changes in renal nitric oxide synthase-3 (NOS3) expression in rats treated with deoxycorticosterone acetate (DOCA) and high salt. All rats were uninephrectomized, and either a placebo or DOCA pellet was implanted subcutaneously. Placebo-treated rats were then given tap water to drink ad libitum, and DOCA-treated rats received a 0.9% NaCl solution to drink. Once a week, rats were placed in metabolic cages so that a 24-h urine sample could be collected. After 3 wk, the animals were sacrificed and the kidneys removed and prepared for subsequent immunohistochemical or Western blot analysis. Urinary excretion of nitrate and nitrite (NOx) was measured to provide an indication of the intrarenal production of NO. DOCA-salt hypertensive rats exhibited increased urinary NOx excretion (2.43 +/- 0.48 micromol NOx/mg creatinine) compared with the placebo control animals (1.17 +/- 0.06 micromol NOx/mg creatinine). Western blot analysis revealed that NOS3 protein levels in both the cortex and medulla were greater in DOCA-salt rats compared with placebo-treated animals. Immunohistochemical analysis of kidneys revealed that NOS3 expression in placebo rats was localized in vascular endothelial cells with slight, but detectable, immunoreactivity in medullary collecting ducts. In DOCA-salt rats, a very large increase in the intensity of immunostaining was detected in tubular epithelia of the proximal tubule, thick ascending limb of Henle's loop, and cortical and medullary collecting duct; immunoreactivity in endothelial cells appeared unchanged. These data suggest that increased tubular expression of NOS3 is responsible, at least in part, for the increased renal production of NO in DOCA-salt hypertension, and are consistent with a role for NO in the renal tubular response to salt loading.
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PMID:Increased nitric oxide synthase-3 expression in kidneys of deoxycorticosterone acetate-salt hypertensive rats. 1054 Dec 86

To evaluate the effect of crude extract of Stevia rebaudiana on renal water, Na+ and K+ excretion, male Wistar rats (250-350 g each) under antidiuresis or water diuresis conditions, were evaluated. During intravenous infusion of the extract (0.05 mg/min/100 g) no significant differences were detected in mean arterial pressure or renal hemodynamics parameters. In contrast, fractional water and sodium excretion and solute clearance increased significantly, in both groups of animals. In antidiuresis rats the extract significantly increased reabsorption of water by the collecting duct and in water diuresis animals the extract significantly increased free water clearance. The data suggest preferential action of the extract in the proximal tubular cells involved with salt transport mechanism.
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PMID:Effect of crude extract of Stevia rebaudiana on renal water and electrolytes excretion. 1058 43

To examine the effect of hydroxyapatite (HAP) seed crystals and urinary macromolecules on the crystallization under conditions similar to those in the collecting duct, we evaporated 100 ml samples of salt solutions with an ion composition assumed to correspond to that in the collecting duct without and with HAP seed crystals. The crystallization in seeded solutions was assessed both with and without dialysed urine (dU). After evaporation the number and volume of crystals were recorded in a Coulter Multisizer and the crystal morphology examined with scanning electron microscopy (SEM) and X-ray crystallography. Addition of HAP crystals was apparently followed by an approximately 15-20% increase in heterogeneous nucleation of calcium oxalate (CaOx). In these experiments SEM and X-ray crystallography showed a high percentage of CaOx in the precipitate. In samples reduced to 40-69 ml, addition of dU to the collecting duct solution containing HAP seed resulted in a greater mean (SD) number of crystals; 3895 (1841) in samples with dU and 1785 (583) in samples without. This was mainly explained by an increased mean (SD) number of small crystals. The mean crystal volume was 17.8 (1.1) and 34.3 (9.1) in samples reduced to 40 69 ml with and without dU, respectively. This might reflect the inhibitory effect of dU on the growth and/or aggregation of the CaOx-CaP precipitate or a promoted nucleation resulting in a large number of small crystals. It is concluded that calcium phosphate formed above the collecting duct might induce heterogeneous nucleation of CaOx at lower levels of the renal collecting system, and that urinary macromolecules are powerful modifiers of these processes.
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PMID:Crystallization during volume reduction of solutions with a composition corresponding to that in the collecting duct: the influence of hydroxyapatite seed crystals and urinary macromolecules. 1065 Nov 29

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

The purpose of this brief commentary is to provide a description of how renal physiology, and more particularly, renal tubular physiology, has evolved over the past thirty years, since the occasion, obviously, is a celebration of the Thirtieth Course on Advances in Nephrology and Dialysis. My arguments will begin by quoting from Homer Smith's book, The Kidney, and merging Smith's observations, which were integrative in the sense that they did not specify detail, with detailed incursions into tubular physiology, first at a cellular level and then at a molecular level. For convenience, the nephron is divided into four functional segments: the proximal nephron; the ascending limb; the distal nephron; and the collecting duct. Each of these carries out a specific function. The proximal nephron absorbs about two-thirds of filtered sodium, without dissociating salt and water absorption. The thick ascending limb absorbs 25% of filtered Na+, but no water. The distal nephron absorbs 10% of filtered Na+ in close relation with K+ and, to some extent, H+ secretion. Finally, the collecting duct includes three kinds of cells: the cortical collecting duct, which is responsible not only for Na+ absorption and K+ secretion, but also for the bulk of the absorption of free water; the outer medullary collecting duct (OMCD), which is largely responsible for the final steep drop in urine pH which occurs between cortex and papilla; and the inner medullary collecting duct (IMCD), whose major function is the final absorption of approximately 5% of filtered Na+.
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PMID:An overview of salt absorption by the nephron. 1068 98

AVP not only increases osmotic water permeability (Pf) in the rat cortical collecting duct (CCD), but also acts synergistically with aldosterone to augment sodium reabsorption (JNa). These effects are inhibited by catecholamines via alpha2 adrenergic receptors, and by dopamine. We review here studies designed to determine the mechanism and receptor involved in dopamine action. The inhibitory effect of dopamine on Na+ and water transport was found to be reversible, and was not produced by agonists specific to D1A and D1B receptors. D2-type (D2, D3 or D4) receptors and activation of the GTP-binding protein Gi were implicated by the observation that dopamine had no inhibitory effect when JNa and Pf were stimulated by a cyclic AMP analogue plus isobutylmethylxanthine. The only dopaminergic antagonist that reversed the inhibitory effect of dopamine was clozapine, which is relatively D4-specific. We also found that dopamine or D1-specific agonists by themselves had no effect on cAMP production. However, dopamine inhibited the high rate of AVP-dependent cAMP production, and this effect of dopamine was reversed by clozapine but not other antagonists or by inhibitors of protein kinase C. The D4 receptor was observed in western blots of renal cortical proteins, and it was localized to the collecting duct by RT-PCR and immuno-histochemistry using a D4-specific antibody. These results show that at least a portion of the natriuretic effect of dopamine can be attributed to inhibition of AVP-dependent Na+ reabsorption by the CCD, and they introduce another signalling system as a candidate in the aetiology of low-renin, salt-dependent hypertension.
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PMID:The collecting duct, dopamine and vasopressin-dependent hypertension. 1069 7

The amiloride-sensitive epithelial sodium channel (ENaC) and the vasopressin-dependent water channel aquaporin-2 (AQP2) mediate mineralocorticoid-regulated sodium- and vasopressin-regulated water reabsorption, respectively. Distributions of ENaC and AQP2 have been shown by immunohistochemistry in rats. Functional data from rabbits suggest a different distribution pattern of these channels than in rats. We studied, by immunohistochemistry in the rabbit kidney cortex, the distributions of ENaC and AQP2, in conjunction with marker proteins for distal segments. In rabbit cortex ENaC is restricted to the connecting tubule (CNT) cells and cortical collecting duct (CCD) cells. The intracellular distribution of ENaC shifts from the apical membrane in the most upstream CNT cells to a cytoplasmic location further downstream in the CNT and in the CCD cells. AQP2 is detected in the CCD cells exclusively. The anatomic subdivisions in the rabbit distal nephron coincide exactly with distributions of apical transport systems. The differences between rabbits and rats in the distribution patterns of ENaC and AQP2 may explain functional differences in renal salt and water handling between these species.
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PMID:Localization of epithelial sodium channel and aquaporin-2 in rabbit kidney cortex. 1075 Dec 13

Hereditary defects in the renal handling of filtered NaCl and water have important implications for understanding the physiological mechanisms that enable the kidney to optimize the match between glomerular filtration rate and tubular reabsorption. Null mutations in the water channel aquaporin 1 (AQP1) or the Na/H exchanger NHE3, two major fluid transporters in the proximal tubule, are states in which a reduction in proximal fluid absorption is accompanied by proportionate decrements in glomerular filtration rate. Compensation of the transport defect by a reduction in filtered load is so efficient that clinically symptomatic Na losses are not observed in either AQPI or NHE3 deficiency. On the other hand, severe syndromes of salt wasting are caused by transport deficiencies in the thick ascending limb or the collecting duct, indicating that the severity of Na dysregulation is unrelated to the basal absorption of NaCl in a given nephron segment. Loss of function of the Na,K,2Cl-cotransporter (NKCC2) or of the epithelial Na channel (ENaC) reduces Na absorption in thick ascending limbs or collecting ducts. In these states, the increased delivery of Na to downstream segments is not monitored by a sensor linked to the site of filtrate formation. In the absence of adaptations in the filtered load, intrarenal compensation of a circumscribed NaCl malabsorption by adjustment of NaCl transport in other nephron segments is remarkably insufficient, particularly in the immature kidney of the newborn.
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PMID:NaCl transport deficiencies--hemodynamics to the rescue. 1078 41


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