scholarly journals In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

2010 ◽  
Vol 299 (6) ◽  
pp. F1473-F1485 ◽  
Author(s):  
Daniel Ackermann ◽  
Nikolay Gresko ◽  
Monique Carrel ◽  
Dominique Loffing-Cueni ◽  
Daniel Habermehl ◽  
...  
Keyword(s):  
Nuclear Localization ◽  
Glucocorticoid Receptors ◽  
Nuclear Translocation ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Plasma Aldosterone ◽  
Thick Ascending Limb ◽  
Cell Nuclei

Aldosterone and corticosterone bind to mineralocorticoid (MR) and glucocorticoid receptors (GR), which, upon ligand binding, are thought to translocate to the cell nucleus to act as transcription factors. Mineralocorticoid selectivity is achieved by the 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) that inactivates 11β-hydroxy glucocorticoids. High expression levels of 11β-HSD2 characterize the aldosterone-sensitive distal nephron (ASDN), which comprises the segment-specific cells of late distal convoluted tubule (DCT2), connecting tubule (CNT), and collecting duct (CD). We used MR- and GR-specific antibodies to study localization and regulation of MR and GR in kidneys of rats with altered plasma aldosterone and corticosterone levels. In control rats, MR and GR were found in cell nuclei of thick ascending limb (TAL), DCT, CNT, CD cells, and intercalated cells (IC). GR was also abundant in cell nuclei and the subapical compartment of proximal tubule (PT) cells. Dietary NaCl loading, which lowers plasma aldosterone, caused a selective removal of GR from cell nuclei of 11β-HSD2-positive ASDN. The nuclear localization of MR was unaffected. Adrenalectomy (ADX) resulted in removal of MR and GR from the cell nuclei of all epithelial cells. Aldosterone replacement rapidly relocated the receptors in the cell nuclei. In ASDN cells, low-dose corticosterone replacement caused nuclear localization of MR, but not of GR. The GR was redistributed to the nucleus only in PT, TAL, early DCT, and IC that express no or very little 11β-HSD2. In ASDN cells, nuclear GR localization was only achieved when corticosterone was replaced at high doses. Thus ligand-induced nuclear translocation of MR and GR are part of MR and GR regulation in the kidney and show remarkable segment- and cell type-specific characteristics. Differential regulation of MR and GR may alter the level of heterodimerization of the receptors and hence may contribute to the complexity of corticosteroid effects on ASDN function.

Localization of kallikrein in the rat kidney and its anatomical relationship to renin.

1982 ◽  
Vol 30 (4) ◽  
pp. 385-390 ◽  
Author(s):  
T B Orstavvik ◽  
T Inagami
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Juxtaglomerular Apparatus ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Afferent Arteriole ◽  
Epitheloid Cells ◽  
Anatomical Relationship

The anatomical relationship between kallikrein and renin in the rat kidney was investigated immunohistochemically by the peroxidase-antiperoxidase method. Kallikrein was localized to the convoluted distal tubule, starting at a point, distal to the juxtaglomerular apparatus, where the thick ascending limb of loop of Henle transformed into the convoluted distal tubule. The thick ascending limb was identified by its content of uromucoid (Tamm-Horsfall glycoprotein). Kallikrein was never observed within the juxtaglomerular apparatus itself. The kallikrein-containing tubule ended where the distal tubule submerged into the collecting duct. Renin was found in epitheloid cells of the afferent arteriole. When neighboring sections were stained for kallikrein and renin, respectively, no close anatomical relationship was observed between the kallikrein-containing and the renin-containing structures.

Peritubular AVP regulates bicarbonate reabsorption in cortical distal tubule via V1 and V2receptors

2002 ◽  
Vol 282 (2) ◽  
pp. F256-F264 ◽  
Author(s):  
Raif Musa-Aziz ◽  
Maria Luisa Morais Barreto-Chaves ◽  
Margarida De Mello-Aires
Keyword(s):  
Receptor Antagonist ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Ion Exchange Resin ◽  
Capillary Perfusion ◽  
Bicarbonate Reabsorption ◽  
Peritubular Capillaries ◽  
Dose Dependent

10.1152/ajprenal.00056.2001. Peritubular arginine vasopressin (AVP) regulates bicarbonate reabsorption in the cortical distal tubule via V1 and V2 receptors. The dose-dependent effects of peritubular AVP on net bicarbonate reabsorption ( J HCO[Formula: see text] ) were evaluated by stationary microperfusion of in vivo early (ED; distal convoluted tubule) and late distal (LD; connecting tubule and initial collecting duct) segments of rat kidney, using double-barreled H+-sensitive, ion-exchange resin/reference (1 M KCl) microelectrodes. AVP (10−11 M) perfused into peritubular capillaries increased J HCO[Formula: see text] , compared with basal levels during intact capillary perfusion with blood, in ED and LD segments. AVP (10−9 M) also increased J HCO[Formula: see text] in both segments, but the effect of AVP (10−11 M) was significantly higher. A specificV1-receptor antagonist alone or with AVP (10−11 or 10−9 M) reduced J HCO[Formula: see text] below basal levels. A specific V2-receptor antagonist alone or plus AVP (10−11 M) did not affect J HCO[Formula: see text] but increased AVP (10−9 M)-mediated stimulation. 8-Bromoadenosine 3′,5′-cyclic monophosphate alone reduced J HCO[Formula: see text] below basal levels and also reduced AVP (10−11 M)-mediated stimulation. (Deamino-Cys1, d-Arg8) vasopressin (a V2-selective agonist) also reduced J HCO[Formula: see text] below basal levels. These results show that peritubular AVP stimulates J HCO[Formula: see text] in ED and LD segments via basolateral V1 receptors and that basolateral V2 receptors have a dose-dependent inhibitory effect mediated by cAMP. The data also indicate that endogenous AVP stimulates distal J HCO[Formula: see text] via basolateral V1 receptors.

Effects of diuretic drugs on Na, Cl, and K transport by rat renal distal tubule

1986 ◽  
Vol 250 (6) ◽  
pp. F1013-F1023 ◽  
Author(s):  
H. Velazquez ◽  
F. S. Wright
Keyword(s):  
Sodium Transport ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Cell Types ◽  
Sodium Absorption ◽  
Thick Ascending Limb ◽  
Chloride Absorption ◽  
Diuretic Drugs ◽  
Potassium Secretion

Diuretic drugs were used to characterize mechanisms involved in transporting sodium, chloride, and potassium across the wall of surface distal tubules of the rat kidney using in vivo microperfusion techniques. Both furosemide and chlorothiazide inhibited sodium and chloride absorption but did not affect the rate of potassium secretion or the transepithelial voltage. However, chlorothiazide inhibited sodium and chloride absorption more completely than furosemide and was additive to the effect of furosemide; furosemide was ineffective if chlorothiazide was already present. In contrast to the effect of furosemide, bumetanide did not affect sodium and chloride absorption but did increase potassium secretion. Amiloride reduced sodium absorption and potassium secretion without affecting net chloride absorption. These effects were additive to those of chlorothiazide. In the loop of Henle bumetanide was more effective than furosemide in inhibiting net sodium potassium and chloride absorption. It appears that cells of the distal tubule in the rat possess an Na-Cl cotransport mechanism that differs from the Na-K-2Cl cotransport mechanism found in the thick ascending limb. Sodium transport also proceeds via a conductive pathway that is inhibited by amiloride. The two modes of sodium transport, conductive and coupled to chloride, may occur in different cell types along the distal tubule.

Role of nitric oxide in the regulation of nephron transport

2002 ◽  
Vol 282 (5) ◽  
pp. F777-F784 ◽  
Author(s):  
Pablo A. Ortiz ◽  
Jeffrey L. Garvin
Keyword(s):  
Nitric Oxide ◽  
Proximal Tubule ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Inhibitory Effect ◽  
Thick Ascending Limb ◽  
In Vivo Experiments ◽  
Osmotic Water ◽  
Direct Inhibitory Effect

Nitric oxide (NO) plays an important role in various physiological processes in the kidney. In vivo experiments first suggested that the natriuretic and diuretic effects caused by NO may be due to decreased NaCl and fluid absorption by the nephron. In the last 10 years, several reports have directly demonstrated a role for NO in modulating transport in different tubule segments. The effects of NO on proximal tubule transport are still controversial. Both stimulation and inhibition of net fluid and bicarbonate have been reported in this segment, whereas only inhibitory effects of NO have been found in Na/H exchanger and Na/K-ATPase activity. The effects of NO in the thick ascending limb are more homogeneous than in the proximal tubule. In this segment, NO decreases net Cl and bicarbonate absorption. A direct inhibitory effect of NO on the Na-K-2Cl cotransporter and the Na/H exchanger has been reported, while NO was found to stimulate apical K channels in this segment. In the collecting duct, NO inhibits Na absorption and vasopressin-stimulated osmotic water permeability. An inhibitory effect of NO on H-ATPase has also been reported in intercalated cells of the collecting duct. Overall, the reported effects of NO in the different nephron segments mostly agree with the natriuretic and diuretic effects observed in vivo. However, the net effect of NO on transport is still controversial in some segments, and in cases like the distal tubule, it has not been studied.

scholarly journals Regulation of epithelial Na+ channels by adrenal steroids: mineralocorticoid and glucocorticoid effects

2012 ◽  
Vol 302 (1) ◽  
pp. F20-F26 ◽  
Author(s):  
Gustavo Frindt ◽  
Lawrence G. Palmer
Keyword(s):  
Glucocorticoid Receptors ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Hormone Treatment ◽  
Surface Expression ◽  
Cortical Collecting Duct ◽  
Epithelial Na Channels ◽  
Independent Effects ◽  
Rate Limiting

Epithelial Na+ channels (ENaC) can be regulated by both mineralocorticoid and glucocorticoid hormones. In the mammalian kidney, effects of mineralocorticoids have been extensively studied, but those of glucocorticoids are complicated by metabolism of the hormones and cross-occupancy of mineralocorticoid receptors. Here, we report effects of dexamethasone, a synthetic glucocorticoid, on ENaC in the rat kidney. Infusion of dexamethasone (24 μg/day) for 1 wk increased the abundance of αENaC 2.26 ± 0.04-fold. This was not accompanied by an induction of Na+ currents ( INa) measured in isolated split-open collecting ducts. In addition, hormone treatment did not increase the abundance of the cleaved forms of either αENaC or γENaC or the expression of βENaC or γENaC protein at the cell surface. The absence of hypokalemia also indicated the lack of ENaC activation in vivo. Dexamethasone increased the abundance of the Na+ transporters Na+/H+ exchanger 3 (NHE3; 1.36 ± 0.07-fold), Na+-K+-2Cl− cotransporter 2 (NKCC2; 1.49 ± 0.07-fold), and Na-Cl cotransporter (NCC; 1.72 ± 0.08-fold). Surface expression of NHE3 and NCC also increased with dexamethasone treatment. To examine whether glucocorticoids could either augment or inhibit the effects of mineralocorticoids, we infused dexamethasone (60 μg/day) together with aldosterone (12 μg/day). Dexamethasone further increased the abundance of αENaC in the presence of aldosterone, suggesting independent effects of the two hormones on this subunit. However, INa was similar in animals treated with dexamethasone+aldosterone and with aldosterone alone. We conclude that dexamethasone can occupy glucocorticoid receptors in cortical collecting duct and induce the synthesis of αENaC. However, this induction is not sufficient to produce an increase in functional Na+ channels in the apical membrane, implying that the abundance of αENaC is not rate limiting for channel formation in the kidney.

Ontogeny of the extracellular calcium-sensing receptor in rat kidney

1996 ◽  
Vol 271 (3) ◽  
pp. F736-F743 ◽  
Author(s):  
N. Chattopadhyay ◽  
M. Baum ◽  
M. Bai ◽  
D. Riccardi ◽  
S. C. Hebert ◽  
...  
Keyword(s):  
Renal Function ◽  
Divalent Cations ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Distal Tubule ◽  
Perinatal Period ◽  
Postnatal Period ◽  
Thick Ascending Limb ◽  
Renal Handling ◽  
Ureteric Buds

We recently cloned extracellular Ca(2+)-sensing receptors (CaRs) from bovine parathyroid and rat kidney that play key roles in Ca2+ homeostasis. Inactivating mutations of the CaR in the inherited human disorder, familial hypocalciuric hypercalcemia, cause reduced responsiveness of the parathyroid to extracellular Ca2+ (Cao2+), as well as abnormally avid renal tubular reabsorption of both Ca2+ and Mg2+ in the distal tubule, suggesting an important role for the CaR in regulating parathyroid hormone (PTH) secretion and renal handling of divalent cations. High Cao2+ also inhibits vasopressinstimulated adenosine 3',5'-cyclic monophosphate accumulation in the medullary thick ascending limb (MTAL) and water reabsorption in the collecting duct (CD) and modulates various other aspects of renal function. The relevance of the CaR to these processes, however, is uncertain. Reduced responsiveness of vasopressin-and PTH-mediated actions on the kidney have been described in the newborn that could potentially reflect effects of the CaR on these aspects of renal function. To define further the role of the CaR in regulating renal function, including the above-mentioned changes during the perinatal period, therefore, we have studied its ontogeny in rat kidney. Northern and Western blot analyses, as well as immunohistochemistry with CaR-specific probes, demonstrate that there is little prenatal expression of the extracellular Ca(2+)-sensing receptor, except in large tubules and branching ureteric buds of developing nephrons. Postnatally, CaR mRNA and protein increase markedly during the 1st wk, related principally to expression of the receptor in the developing TAL and, to a lesser extent, in the CD. The level of expression of the receptor remains nearly constant after postnatal day 14. These results demonstrate that the perinatal increases in expression of CaR mRNA and protein parallel its tissue-specific renal expression. Furthermore, it is possible that some of the previously described changes in renal handling of divalent cations and water in the perinatal and immediate postnatal period are related, in part, to the increasing levels of expression of the CaR and resultant inhibitory effects on the actions of PTH and antidiuretic hormone on the developing nephron.

scholarly journals Primary Gene Structure and Expression Studies of Rodent Paracellin-1

2001 ◽  
Vol 12 (12) ◽  
pp. 2664-2672 ◽  
Author(s):  
Stefanie Weber ◽  
Karl P. Schlingmann ◽  
Melanie Peters ◽  
Lene Niemann Nejsum ◽  
Søren Nielsen ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Rat Kidney ◽  
Genomic Structure ◽  
Distal Tubule ◽  
Thick Ascending Limb ◽  
Putative Open Reading Frame ◽  
Reading Frame ◽  
Henle's Loop ◽  
Junction Protein ◽  
Gene Structure And Expression

ABSTRACT. The novel member of the claudin multigene family, paracellin-1/claudin-16, encoded by the genePCLN1, is a renal tight junction protein that is involved in the paracellular transport of magnesium and calcium in the thick ascending limb of Henle’s loop. Mutations in humanPCLN1are associated with familial hypomagnesemia with hypercalciuria and nephrocalcinosis, an autosomal recessive disease that is characterized by severe renal magnesium and calcium loss. The complete coding sequences of mouse and ratPcln1and the murine genomic structure are here presented. Full-length cDNAs are 939 and 1514 bp in length in mouse and rat, respectively, encoding a putative open-reading frame of 235 amino acids in both species with 99% identity. Exon-intron analysis of the human and mouse genes revealed a 100% homology of coding exon lengths and splice-site loci. By radiation hybrid mapping, the murinePcln1gene was assigned directly to marker D16Mit133 on mouse chromosome 16 (syntenic to a locus on human chromosome 3q27, which harbors the humanPCLN1gene). Mouse multiple-tissue Northern blot showedPcln1expression exclusively in the kidney. The expression profile along the nephron was analyzed by reverse transcriptase-PCR on microdissected nephron segments and immunohistochemistry of rat kidney. Paracellin-1 expression was restricted to distal tubular segments including the thick ascending limb of Henle’s loop, the distal tubule, and the collecting duct. The identification and characterization of the rodentPcln1genes provide the basis for further studies of paracellin-1 function in suitable animal models.

Abnormal postpartum renal development and cystogenesis in the bcl-2 (-/-) mouse

1996 ◽  
Vol 271 (1) ◽  
pp. F184-F193 ◽  
Author(s):  
C. M. Sorenson ◽  
B. J. Padanilam ◽  
M. R. Hammerman
Keyword(s):  
Cellular Proliferation ◽  
Kidney Development ◽  
Apoptotic Cell ◽  
Collecting Duct ◽  
Distal Tubule ◽  
Renal Development ◽  
Thick Ascending Limb ◽  
Renal Hypoplasia ◽  
Cellular Origin ◽  
Bax Protein

Mice deficient for B cell leukemia/lymphoma gene 2 [bcl-2(-/-) mice] manifest congenital renal hypoplasia and develop multicystic kidney disease and renal failure postnatally. To characterize postpartum renal development, to identify the cellular origin of the cysts, and to provide insight into the role that bcl-2 deficiency plays in the cystogenic process, we examined the morphology of kidneys from bcl-2 (-/-) mice and wild-type littermates [bcl-2 (+/+)] from birth (P0) to postpartum day 28 (P28), determined whether abnormalities of cellular proliferation and apoptosis accompany cyst development, and characterized expression of the bcl-2-related protein, bax. Between P0 and P7, kidneys from bcl-2 (-/-) and bcl-2 (+/+) mice undergo a comparable increase in weight and have similar histological appearances. However, during the next 2 wk of life, weight gain in kidneys from bcl-2 (-/-) mice is reduced compared with that in kidneys from bcl-2 (+/+) animals, and cysts develop in tubules with staining characteristics of proximal tubule, distal tubule/medullary thick ascending limb of Henle's loop, and collecting duct. Unaffected glomeruli and proximal tubules in kidneys of bcl-2 (-/-) mice undergo compensatory growth. Cystogenesis is accompanied by enhanced incorporation of 5-bromo-2'-deoxyuridine in cells within cortex and medulla and apoptosis of cells within cysts and in the renal interstitium. Bax protein is expressed in the distal tubule in kidneys of bcl-2 (+/+) and bcl-2 (-/-) mice and in some, but not all cysts. We conclude that abnormal regulation of DNA synthesis and apoptosis accompany cystogenesis in bcl-2 (-/-) mice during postpartum kidney development. Continued expression of bax could enhance apoptotic cell death.0

scholarly journals Differential Expression Patterns of Claudins, Tight Junction Membrane Proteins, in Mouse Nephron Segments

2002 ◽  
Vol 13 (4) ◽  
pp. 875-886 ◽  
Author(s):  
Yumiko Kiuchi-Saishin ◽  
Shimpei Gotoh ◽  
Mikio Furuse ◽  
Akiko Takasuga ◽  
Yasuo Tano ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Tight Junction ◽  
Polyclonal Antibodies ◽  
Collecting Duct ◽  
Expression Patterns ◽  
Distal Tubule ◽  
Northern Blotting ◽  
Thick Ascending Limb ◽  
Specific Expression ◽  
Nephron Segments

ABSTRACT. As the first step in understanding the physiologic functions of claudins (tight junction integral membrane proteins) in nephrons, the expression of claudin-1 to -16 in mouse kidneys was examined by Northern blotting. Among these claudins, only claudin-6, -9, -13, and -14 were not detectable. Claudin-5 and -15 were detected only in endothelial cells. Polyclonal antibodies specific for claudin-7 and -12 were not available. Therefore, the distributions of claudin-1, -2, -3, -4, -8, -10, -11, and -16 in nephron segments were examined with immunofluorescence microscopy. For identification of individual segments, antibodies specific for segment markers were used. Immunofluorescence microscopic analyses of serial frozen sections of mouse kidneys with polyclonal antibodies for claudins and segment markers revealed that claudins demonstrated very complicated, segment-specific, expression patterns in nephrons, i.e., claudin-1 and -2 in Bowman’s capsule, claudin-2, -10, and -11 in the proximal tubule, claudin-2 in the thin descending limb of Henle, claudin-3, -4, and -8 in the thin ascending limb of Henle, claudin-3, -10, -11, and -16 in the thick ascending limb of Henle, claudin-3 and -8 in the distal tubule, and claudin-3, -4, and -8 in the collecting duct. These segment-specific expression patterns of claudins are discussed, with special reference to the physiologic functions of tight junctions in nephrons.

Urodilatin: binding properties and stimulation of cGMP generation in rat kidney cells

1993 ◽  
Vol 264 (2) ◽  
pp. F267-F273
Author(s):  
H. Saxenhofer ◽  
W. R. Fitzgibbon ◽  
R. V. Paul
Keyword(s):  
Guanylate Cyclase ◽  
Mesangial Cells ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Binding Characteristics ◽  
Papillary Collecting Duct ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct ◽  
Anp Receptors

Urodilatin (URO) [ANP-(95-126)] is an analogue of atrial natriuretic peptide (alpha-ANP) [ANP-(99-126)] that was first isolated from human urine. In rat mesangial cells, URO competed with high affinity for non-guanylate cyclase-coupled ANPR-C receptors [concentration at which 50% labeled ligand is displaced (IC50) approximately 70 pM], but with lesser affinity to the guanylate cyclase-linked ANPR-A receptors (IC50 approximately 800 pM). alpha-ANP bound to both receptors with similar affinity [dissociation constant (Kd) approximately 150 pM]. In papillary collecting duct homogenates, which possess only ANPR-A receptors, the apparent Kd value averaged 229 pM for alpha-ANP and 2.7 nM for URO. Intravenous URO was at least as potent and effective as alpha-ANP in inducing diuresis and natriuresis in anesthetized rats, but URO was approximately 10-fold less potent in stimulating guanosine 3',5'-cyclic monophosphate generation in mesangial and inner medullary collecting duct cells. We conclude that URO has a lesser affinity than alpha-ANP for guanylate cyclase-coupled ANP receptors in the kidney and that the relative natriuretic potency of URO in vivo cannot be directly attributed to its binding characteristics with ANPR-A receptors.

Sign in / Sign up

Export Citation Format

Share Document