hPTH-fragments (53-84) and (28-48) antagonize the stimulation of calcium release and repression of alkaline phosphatase activity by hPTH-(1-34) in vitro.
Different C-terminal fragments of parathyroid hormone (PTH)-(1-84) in blood participate in the regulation of calcium homeostasis by PTH-(1-84), and an antagonizing effect for the large carboxyl-terminal parathyroid hormone (C-PTH)-fragment (7-84) on calcium release has been described in vivo and in vitro. In this study the smaller C-PTH-fragment (53-84) and mid-regional PTH fragment (28-48), which represent discrete areas of activity in the PTH-(7-84) molecule, were assayed for their effects on calcium release and alkaline phosphatase (ALP) activity in a chick bone organ culture system. Neither PTH-(28-48) nor PTH-(53-84) had any effect on calcium release into the medium and both fragments stimulated ALP activity in the bone tissue, suggesting that the cAMP/PKA signalling pathway was not affected by these fragments. However they suppressed the calcium release induced by PTH-(1-34) and attenuated the down regulation of ALP activity caused by PTH-(1-34), suggesting that the effect on the cAMP/PKA signalling pathway may be indirectly. In conclusion, the study shows that the PTH-fragments (53-84) and (28-48) antagonize the PTH-(1-34) induced effects on calcium release and inhibition of ALP activity in a chick bone organ culture system.
Duvos
Christian
C
German Research Centre for Biotechnology, Department of Gene Regulation and Differentiation, Mascheroderwag 1, D-38124 Braunschweig, Germany.
Scutt
Andrew
A
Mayer
Hubert
H
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002642:Chick Embryo; D000242:Cyclic AMP / Q000378:metabolism; D004336:Drug Antagonism; D006801:Humans; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D015398:Signal Transduction; D019379:Teriparatide / Q000031:analogs & derivatives* / Q000494:pharmacology; D013977:Tibia / Q000166:cytology / Q000378:metabolism
D010281:Parathyroid Hormone; D010446:Peptide Fragments; C069678:parathyroid hormone (28-48); C035453:parathyroid hormone (53-84); D019379:Teriparatide; D000242:Cyclic AMP; D000469:Alkaline Phosphatase; C035748:parathyroid hormone (1-34)amide; D002118:Calcium