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.

Heat stress protein-associated cytoprotection of inner medullary collecting duct cells from rat kidney

1993 ◽  
Vol 265 (3) ◽  
pp. F333-F341 ◽  
Author(s):  
S. C. Borkan ◽  
A. Emami ◽  
J. H. Schwartz
Keyword(s):  
Heat Stress ◽  
Thermal Injury ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Metabolic Effects ◽  
Lactate Dehydrogenase Activity ◽  
Inner Medullary Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct

Although heat stress proteins (HSPs) mediate thermotolerance, the cellular targets of thermal injury and mechanisms of acquired cytoprotection are unknown. To describe the metabolic effects of hyperthermia and the potential mechanisms of thermotolerance, the following were measured in inner medullary collecting duct cells after a 43 degrees C and/or a 50 degrees C thermal insult: 1) state III mitochondrial respiration (SIII MR), 2) glycolytic rate, 3) lactate dehydrogenase activity, 4) membrane permeability, and 5) HSP 72 content. Compared with controls incubated at 37 degrees C, cells heated to 50 degrees C showed a 30 and 50% reduction in glycolysis and SIII MR, respectively. After heating to 50 degrees C, the cell membrane remained intact and immunoreactive HSP 72 was not detected. In contrast, heating to 43 degrees C induced accumulation of HSP 72 and transiently increased both SIII MR and glycolysis. In addition, prior exposure to 43 degrees C completely prevented the fall in SIII MR and glycolysis anticipated with a subsequent 50 degrees C insult. Cytoprotection gradually diminished over several days and correlated with the disappearance of HSP 72. Preservation of oxidative and anaerobic metabolism associated with HSPs may be important in developing resistance to thermal injury.

scholarly journals Transcriptional profiling of native inner medullary collecting duct cells from rat kidney

2008 ◽  
Vol 32 (2) ◽  
pp. 229-253 ◽  
Author(s):  
Panapat Uawithya ◽  
Trairak Pisitkun ◽  
Brian E. Ruttenberg ◽  
Mark A. Knepper
Keyword(s):  
Signal Intensity ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Transcriptional Profiling ◽  
High Signal ◽  
Inner Medullary Collecting Duct ◽  
Duct Cells ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct ◽  
V2 Vasopressin Receptor

Vasopressin acts on the inner medullary collecting duct (IMCD) in the kidney to regulate water and urea transport. To obtain a “parts list” of gene products expressed in the IMCD, we carried out mRNA profiling of freshly isolated rat IMCD cells using Affymetrix Rat 230 2.0 microarrays with ∼31,000 features; 7,913 annotated transcripts were found to be expressed above background in the IMCD cells. We have created a new online database (the “IMCD Transcriptome Database;” http://dir.nhlbi.nih.gov/papers/lkem/imcdtr/ ) to make the results publicly accessible. Among the 30 transcripts with the greatest signals on the arrays were 3 water channels: aquaporin-2, aquaporin-3, and aquaporin-4, all of which have been reported to be targets for regulation by vasopressin. In addition, the transcript with the greatest signal among members of the solute carrier family of genes was the UT-A urea transporter ( Slc14a2), which is also regulated by vasopressin. The V2 vasopressin receptor was strongly expressed, but the V1a and V1b vasopressin receptors did not produce signals above background. Among the 200 protein kinases expressed, the serum-glucocorticoid-regulated kinase ( Sgk1) had the greatest signal intensity in the IMCD. WNK1 and WNK4 were also expressed in the IMCD with a relatively high signal intensity, as was protein kinase A (β-catalytic subunit). In addition, a large number of transcripts corresponding to A kinase anchoring proteins and 14-3-3 proteins (phospho-S/T-binding proteins) were expressed. Altogether, the results combine with proteomics studies of the IMCD to provide a framework for modeling complex interaction networks responsible for vasopressin action in collecting duct cells.

Direct fibrogenic effects of aldosterone on normotensive kidney: an effect modified by 11β-HSD activity

2010 ◽  
Vol 298 (5) ◽  
pp. F1178-F1187 ◽  
Author(s):  
Andrew S. Brem ◽  
David J. Morris ◽  
Yan Ge ◽  
Lance Dworkin ◽  
Evelyn Tolbert ◽  
...  
Keyword(s):  
Collecting Duct ◽  
Tissue Growth ◽  
Proximal Tubule Cells ◽  
Ru 486 ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct ◽  
Induced Changes ◽  
Rat Proximal Tubule ◽  
Sirius Red

Aldosterone (Aldo) can be a profibrotic factor in cardiovascular and renal tissues. This study tests the hypothesis that prolonged Aldo exposure is able to directly induce fibrotic changes in the kidney of a normal nonhypertensive animal. Immortalized rat proximal tubule cells (IRPTC) containing 11β-hydroxysteroid dehydrogenase (11β-HSD1) but no mineralocorticoid receptors (MR) and mouse inner medullary collecting duct cells (IMCD) containing 11β-HSD2 and MR were examined. IRPTC exposed to Aldo or corticosterone (10 nM) for 48 h demonstrated no change in collagen production as assessed by Sirius red staining. In contrast, IMCD treated with Aldo exhibited a marked increase in the expression of collagen, fibronectin, and connective tissue growth factor (CTGF), whereas corticosterone alone had no effect. The Aldo-induced overexperession of collagen, fibronectin, and CTGF was substantially attenuated by the MR antagonist RU-318 and by the 11β-HSD end product 11-dehydrocorticosterone, but not by the glucocorticoid receptor antagonist RU-486. In vivo, early fibrotic changes with elevated collagen, fibronectin, and CTGF expression were observed in kidneys isolated from normotensive adrenalectomized mice receiving a continuous infusion of Aldo (8 μg·kg−1·day−1) for 1 wk. These changes were not present in corticosterone-treated mice. Aldo-induced changes were attenuated in adrenally intact mice and in mice treated with RU-318 or 11-dehydrocorticosterone. Thus, extended Aldo exposure produces fibrotic changes in cells containing MR and in normal kidneys. MR antagonists and the end products of 11β-HSD attenuate these fibrogenic effects.

scholarly journals Monitoring urea transport in rat kidney in vivo using hyperpolarized 13C magnetic resonance imaging

2012 ◽  
Vol 302 (12) ◽  
pp. F1658-F1662 ◽  
Author(s):  
Cornelius von Morze ◽  
Robert A. Bok ◽  
Jeff M. Sands ◽  
John Kurhanewicz ◽  
Daniel B. Vigneron
Keyword(s):  
Magnetic Resonance Imaging ◽  
Magnetic Resonance ◽  
Nuclear Polarization ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Resonance Imaging ◽  
Hyperpolarized 13C ◽  
New Methods ◽  
Medullary Collecting Duct

Urea functions as a key osmolyte in the urinary concentrating mechanism of the inner medulla. The urea transporter UT-A1 is upregulated by antidiuretic hormone, facilitating faster equilibration of urea between the lumen and interstitium of the inner medullary collecting duct, resulting in the formation of more highly concentrated urine. New methods in dynamic nuclear polarization, providing ∼50,000-fold enhancement of nuclear magnetic resonance signals in the liquid state, offer a novel means to monitor this process in vivo using magnetic resonance imaging. In this study, we detected significant signal differences in the rat kidney between acute diuretic and antidiuretic states, using dynamic 13C magnetic resonance imaging following a bolus infusion of hyperpolarized [13C]urea. More rapid medullary enhancement was observed under antidiuresis, consistent with known upregulation of UT-A1.

Brain natriuretic peptide: interaction with renal ANP system

1990 ◽  
Vol 258 (3) ◽  
pp. F467-F472
Author(s):  
M. Gunning ◽  
B. J. Ballermann ◽  
P. Silva ◽  
B. M. Brenner ◽  
M. L. Zeidel
Keyword(s):  
Molecular Weight ◽  
Brain Natriuretic Peptide ◽  
Natriuretic Peptide ◽  
Guanylate Cyclase ◽  
Collecting Duct ◽  
Ring Structure ◽  
High Affinity ◽  
Medullary Collecting Duct ◽  
22Na Uptake ◽  
Anp Receptors

Brain natriuretic peptide (BNP) has recently been found in porcine brain and has been shown to cause diuresis and natriuresis when injected in rats, effects similar to those caused by atrial natriuretic peptide (ANP). BNP is also synthesized in the cardiac atria and circulates in plasma. The amino acid sequence of the peptide resembles that of ANP particularly closely within the ring structure of the peptide. We examined the potential role of BNP in modulating renal function by assessing its ability to mimic the effects of ANP on rat glomeruli and in rabbit inner medullary collecting duct cells (IMCD). BNP bound with high affinity to glomeruli (Kd approximately 900 pM) and IMCD cells (Kd approximately 500 pM). In IMCD cells, BNP stimulated particulate guanylate cyclase (approximately 3-fold at maximum ligand concentration) and inhibited conductive 22Na+ uptake by 50% at concentrations at which ANP is also effective. In rat glomeruli, BNP bound with high affinity to the low-molecular-weight receptors but with lesser affinity to the higher-molecular-weight guanylate cyclase-linked receptors (Kd approximately 50 nM). In addition, the guanosine 3',5'-cyclic monophosphate accumulation response was less impressive in glomeruli than the guanylate cyclase response in IMCD tissue. Thus we conclude that BNP is of only slightly reduced affinity and potency for the ANP receptors in the kidney and probably acts through these receptors to exert its physiological effects.

Low pH enhances expression of carbonic anhydrase II by cultured rat inner medullary collecting duct cells

1994 ◽  
Vol 266 (2) ◽  
pp. C508-C514 ◽  
Author(s):  
G. J. Schwartz ◽  
D. Brown ◽  
R. Mankus ◽  
E. A. Alexander ◽  
J. H. Schwartz
Keyword(s):  
Carbonic Anhydrase ◽  
Collecting Duct ◽  
Rat Kidney ◽  
Northern Analysis ◽  
Human Antibody ◽  
Inner Medullary Collecting Duct ◽  
Coding Regions ◽  
Steady State Levels ◽  
Collecting Duct Cells ◽  
Medullary Collecting Duct

Carbonic anhydrase (CA) facilitates the secretion of protons from renal epithelia by catalyzing the buffering of hydroxyl ions by CO2. We have previously found that inner medullary collecting duct (IMCD) cells cultured from rat kidney secrete protons and express CA II. Incubation of IMCD cells in acidic medium for 48 h has been shown to stimulate the secretion of protons by a protein synthesis-dependent process. To establish whether CA II might be involved in this process, IMCD cells were exposed to incubation media supplemented with 10(-7) M deoxycorticosterone acetate, pH 7.0 (acid) or pH 7.7 (control) for 48 h, and CA II mRNA and protein were quantitated. Part of the CA II cDNA was obtained by reverse transcription of total RNA from rat kidney followed by amplification using oligonucleotide primers derived from conserved areas in the coding regions of human, mouse, and chick CA II cDNAs in a polymerase chain reaction. By Northern analysis, steady-state levels of CA II mRNA from acid-incubated cells showed an increase of 80% compared with controls and 70% when expressed relative to a housekeeping mRNA, beta-actin. Western blot analysis using a human antibody to CA II showed an approximate doubling of CA II protein after acid incubation. By immunofluorescence microscopy, the domes of acid-incubated IMCD cells contained considerably more CA II-stained cells than found in control cultures. Thus incubation of IMCD cells in acid medium stimulates the expression of CA II mRNA and protein.(ABSTRACT TRUNCATED AT 250 WORDS)

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