The renal PTH/PTHrP receptor is down-regulated in rats with chronic renal failure.
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)
Ureña
P
P
INSERM Unité 90, Hôpital Necker, Paris, France.
Kubrusly
M
M
Mannstadt
M
M
Hruby
M
M
Trinh
M M
MM
Silve
C
C
Lacour
B
B
Abou-Samra
A B
AB
Segre
G V
GV
Drüeke
T
T
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*
D015335:Molecular Probes; D012333:RNA, Messenger; D044168:Receptor, Parathyroid Hormone, Type 1; D018016:Receptors, Parathyroid Hormone; D000262:Adenylyl Cyclases