Action of tumoral PTH-related peptide on phosphate and calcium transport.
The recently identified parathyroid hormone-related peptide (PTHrP) exerts several actions on the transport of bone mineral elements. In vitro, the effects of the synthetic amino-terminal fragment of the parathyroid hormone-related protein PTHrP (1-34) on renal cyclic AMP production, Na-dependent Pi transport and Na+/H+ exchange appear to be very similar to PTH (1-34). In vivo, in thyroparathyroidectomized rats, PTHrP reduces the tubular Pi reabsorptive capacity (TmPi/GFR) and thereby lowers the level of plasma Pi. PTHrP (1-34) brings about a dose-dependent elevation in the level of plasma Ca. The hypercalcemic effect of PTHrP (1-34) is due to both an increase in bone Ca resorption, as assessed by an increment in fasting urinary Ca, and an elevation in renal Ca reabsorption. Like PTH, the tumoral peptide does not significantly affect the overall tubular reabsorption of Na. The PTHrP-induced increase in bone Ca resorption is completely inhibitable by diphosphonate therapy. Despite this efficacious antiosteolytic response the fall in calcemia is moderate since the marked effect of PTHrP on the renal transport of Ca is maintained under diphosphonate therapy. These experimental findings are similar to clinical observations previously made with several types of solid tumors.
Bonjour
J P
JP
Department of Medicine, University Hospital, Geneva, Switzerland.
Rizzoli
R
R
Pizurki
L
L
Caverzasio
J
J
D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D006934:Hypercalcemia / Q000209:etiology; D007684:Kidney Tubules / Q000378:metabolism; D009363:Neoplasm Proteins / Q000494:pharmacology; D009369:Neoplasms / Q000150:complications / Q000378:metabolism*; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism*; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D017923:Sodium-Hydrogen Exchangers; D015291:Transforming Growth Factors / Q000494:pharmacology
D002352:Carrier Proteins; D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D010710:Phosphates; D011506:Proteins; D017923:Sodium-Hydrogen Exchangers; C054296:parathyroid hormone-related protein (1-34); D015291:Transforming Growth Factors; D000242:Cyclic AMP; D002118:Calcium