Abstract: Publisher Summary This chapter discusses the parathyroid hormone and its receptors. Parathyroid hormone (PTH) is synthesized in the parathyroid cells as a pre-pro-hormone comprised of 115 amino acids. The signal peptide of PTH allows translocation of the polypeptide into the secretory vesicles, a property that is shared with most secreted proteins. Parathyroid hormone-related peptide (PTHrP) was characterized from malignant tumors that cause hypercalcemia in cancer patients. PTHrP has significant sequence homology to PTH that is limited to its 13 aminoterminal residues. However, this limited sequence homology allows high binding affinity and full activation of the PTH receptor by PTHrP. The molecular cloning of a single receptor from bone and kidney that equivalently binds PTH and PTHrP ultimately proved that one single receptor molecule binds both ligands. The cloned receptor is therefore named the PTH/PTHrP receptor. Attempts to purify the PTH/PTHrP receptor from renal membranes and osteosarcoma cell lines are not successful. The main obstacle is the inability to solubulize large quantities of functional PTH receptor molecules. The PTH/PTHrP receptor from rat, mouse, opossum, human, and Xenopus , expressed in COS-7 cells, binds PTH( 1-34) and PTHrP( 1-36) with high affinity with K d s in the nM range (10 nM). PTH is known to stimulate CAMP accumulation in its target cells. Maintenance of extracellular calcium homeostasis involves regulation of the responsiveness of the target cells to PTH by the hormonal milieu.
Publication Year: 1998
Publication Date: 1998-01-01
Language: en
Type: book-chapter
Indexed In: ['crossref']
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Cited By Count: 1
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