The renal PTH/PTHrP receptor is down-regulated in rats with chronic renal failure

摘要: The renal PTH/PTHrP receptor is down-regulated in rats with chronic failure. Hypocalcemia, hyperphosphatemia, and resistance to the action of PTH are well characterized features setting advanced failure (CRF). Although underlying mechanisms ill-understood, clinical experimental evidence points both down-regulation post-receptor abnormalities their pathogenesis. In present study we have examined effect CRF on expression (PTH-R). was created by a standard two-step operation (5/6 nephrectomy). Four weeks thereafter, 19 uremic were compared 23 sham-operated rats. Uremic had higher mean (± SD) plasma creatinine levels than control rats, 164 ± 107 µM versus 43 5 µM, respectively. They also phosphorus iPTH levels, 4.70 1.71mM 2.59 0.37mM 561 336 27 18 pg/ml, Mean total calcium blood ionized significantly lower 2.13 0.06mM 2.61 0.10mM 1.07 0.11 1.31 ±0.06mM, calcitriol concentration 39.8 14.6 80.4 15.2 Nine out for PTH-R gene expression. We show first time that level mRNA kidney markedly decreased normal ratio mRNA/β-actin being 0.47 0.12 0.99 0.23, respectively, mRNA/28S 8.9 4.7 19.6 11.1, This decrease associated marked reduction PTH-sensitive adenylyl cyclase activity crude membranes from values basal subsequently after stimulation forskolin NaF reduced comparison These data indicate severe expression, diminished activity. could be important pathogenesis secondary hyperparathyroidism CRF.