title: The renal PTH/PTHrP receptor is down-regulated in rats with chronic renal failure.
abstract: Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features in the setting of advanced chronic renal failure (CRF). Although the underlying mechanisms are ill-understood, clinical and experimental evidence points to both PTH receptor down-regulation and post-receptor abnormalities in their pathogenesis. In the present study we have examined the effect of advanced CRF in rats on the renal expression of PTH/PTHrP receptor (PTH-R). CRF was created by a standard two-step operation (5/6 nephrectomy). Four weeks thereafter, 19 uremic rats were compared with 23 sham-operated rats. Uremic rats had higher mean (+/- SD) plasma creatinine levels than control rats, 164 +/- 107 microM versus 43 +/- 5 microM, respectively. They also had higher plasma phosphorus and iPTH levels, 4.70 +/- 1.71 mM versus 2.59 +/- 0.37 mM and 561 +/- 336 versus 27 +/- 18 pg/ml, respectively. Mean plasma total calcium and blood ionized calcium were significantly lower in uremic than in control rats, 2.13 +/- 0.06 mM versus 2.61 +/- 0.10 mM and 1.07 +/- 0.11 versus 1.31 +/- 0.06 mM, respectively. Mean plasma calcitriol concentration was also significantly lower in uremic than in control rats, 39.8 +/- 14.6 and 80.4 +/- 15.2 pg/ml, respectively. Nine out of the 19 rats were examined for renal PTH-R gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: INSERM Unité 90, Hôpital Necker, Paris, France.
authors.forename: P
authors.initials: P
authors.lastname: Ureña
authors.forename: M
authors.initials: M
authors.lastname: Kubrusly
authors.forename: M
authors.initials: M
authors.lastname: Mannstadt
authors.forename: M
authors.initials: M
authors.lastname: Hruby
authors.forename: M M
authors.initials: MM
authors.lastname: Trinh
authors.forename: C
authors.initials: C
authors.lastname: Silve
authors.forename: B
authors.initials: B
authors.lastname: Lacour
authors.forename: A B
authors.initials: AB
authors.lastname: Abou-Samra
authors.forename: G V
authors.initials: GV
authors.lastname: Segre
authors.forename: T
authors.initials: T
authors.lastname: Drüeke
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D015536:Down-Regulation; D007668:Kidney / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism*; D008297:Male; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000378:metabolism*
chemical_list: D015335:Molecular Probes; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D000262:Adenylyl Cyclases