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      Mechanisms of Down-Regulation of the Renal Parathyroid Hormone Receptor in Rats with Chronic Renal Failure

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          Hypocalcemia, hyperphosphatemia and resistance to the action of parathyroid hormone (PTH) are well-characterized features in advanced chronic renal failure (CRF). Their pathogenesis has been attributed to both PTH receptor (PTH-R) down-regulation and postreceptor abnormalities. In this study, we examined the renal expression of the PTH-R mRNA in CRF (5/6 nephrectomy) rats. Experiments were also performed to determine whether an acidic condition and PTH itself influence PTH-R mRNA expression. RT-competitive PCR was used to examine mRNA expression, and polyclonal antibody against PTH-R was used for Western blot. PTH-R mRNA expression was abundant in glomeruli, proximal convoluted and straight tubules (PCT, PST), small in medullary and cortical thick ascending limbs, and cortical collecting ducts and not detectable in outer and inner medullary collecting ducts. The expression was significantly decreased in PCT and PST in CRF rats. Decrease in PTH-R mRNA expression was observed 1 week after the induction of CRF. PTH-R protein was decreased at 2 (–23%) and 4 (–45%) weeks in renal cortex, but not in medulla in CRF rats. PTH-R mRNA expression in PST was decreased by low pH (7.1 or 6.7) incubation compared with that at pH 7.4. PTH(1–34) (10<sup>–9</sup>  M) increased PTH-R mRNA expression in PST from control rats by 250%. The stimulatory effect of PTH on PTH-R mRNA expression was decreased by the incubation at low pH medium. In summary, renal PTH-R is down-regulated in CRF rats. The decrease in mRNA expression in PCT and PST causes the decrease in PTH-R protein. Metabolic acidosis may participate in the down-regulation of PTH-R in early stage of CRF. This abnormality could be important in the pathogenesis of secondary hyperparathyroidism of CRF.

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          Intranephron localization and regulation of the V1a vasopressin receptor during chronic metabolic acidosis and dehydration in rats.

          The intrarenal localization and role of the V1a vasopressin receptor in body fluid homeostasis are unclear. We investigated the intranephron localization of V1a receptor mRNA and protein using reverse transcription (RT)-competitive polymerase chain reaction (PCR) and immunohistochemistry with a specific polyclonal antibody. To determine whether the V1a receptor is involved in the regulation of acid-base balance, we also examined the effects of acute and chronic metabolic acidosis and dehydration on V1a receptor expression. V1a mRNA was expressed most abundantly in the cortical collecting ducts (CCD) and decreased in the deeper CD. Expression in the glomeruli and thick ascending limbs was low. The immunohistochemical study revealed the presence of the V1a receptor in the glomeruli, the thick ascending limbs and the CD. Dehydration decreased V1a mRNA expression in the CD. Chronic metabolic acidosis increased V1a receptor mRNA expression in the CD but decreased V2 receptor mRNA expression. Western blot analysis revealed up-regulation of the V1a receptor protein in chronic metabolic acidosis. Incubation of microdissected CCD or outer medullary CD (OMCD) in a low-pH (or or low-HCO3-) medium increased the levels of V1a receptor mRNA but decreased V2 receptor mRNA expression. Incubating OMCD with arginine vasopressin (AVP) and the V1a receptor antagonist (OPC21268) increased V2 receptor mRNA expression compared with incubation with AVP alone. These data suggest that V1a receptors are present primarily in the principal and intercalated cells in the CD and that these receptors are involved in the regulation of water and acid-base balance.
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            Cloning of a Parathyroid Hormone/Parathyroid Hormone-Related Peptide Receptor (PTHR) cDNA from a Rat Osteosarcoma (UMR 106) Cell Line: Chromosomal Assignment of the Gene in the Human, Mouse, and Rat Genomes

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              Expression of alternatively spliced isoforms of the parathyroid hormone (PTH)/PTH-related peptide receptor messenger RNA in human kidney and bone cells

               A. S. Jobert (1996)

                Author and article information

                Nephron Exp Nephrol
                Cardiorenal Medicine
                S. Karger AG
                April 2003
                17 November 2004
                : 93
                : 4
                : e141-e149
                Third Department of Internal Medicine, Kumamoto University School of Medicine, Honjo, Kumamoto, Japan
                70238 Nephron Exp Nephrol 2003;93:e141–e149
                © 2003 S. Karger AG, Basel

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                Page count
                Figures: 5, Tables: 1, References: 29, Pages: 1
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/70238
                Original Paper


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