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Inhibition of in vitro bone resorption by a parathyroid hormone receptor antagonist in the canine adenocarcinoma model of humoral hypercalcemia of malignancy.

Abstract
In vitro bone resorption induced by tumor extract derived from a hypercalcemic canine adenocarcinoma was significantly inhibited by the PTH receptor antagonist, [Nle8,18,Tyr34]bovine (b) PTH-(3-34) amide. Dose-response curves were prepared for in vitro bone resorption induced in neonatal mouse calvaria by tumor extract, bPTH-(1-34), and prostaglandin E2. A 1:2000-fold ratio of bPTH-(1-34) to [Nle8,18,Tyr34]bPTH-(3-34) amide significantly inhibited bone resorption induced by bPTH-(1-34); however, a 1:10,000 ratio completely antagonized bone resorption. At equivalent potency (1.80-fold stimulation of in vitro bone resorption) of tumor extract compared to bPTH-(1-34), [Nle8,18,Tyr34]bPTH-(3-34) amide (5.0 microM) was capable of significantly reducing in vitro bone resorption. Bone resorption induced by tumor extract (1.35-fold stimulation) was inhibited by [Nle8,18,Tyr34]bPTH-(3-34) amide at concentrations of 5.0 and 1.0 microM. Bone resorption induced by prostaglandin E2 (300 nM) was not inhibited by [Nle8,18,Tyr34]bPTH-(3-34) amide (5.0 microM). These data indicate that [Nle8,18,Tyr34]bPTH-(3-34) amide antagonizes in vitro bone resorption induced by bPTH-(1-34) in a dose-dependent manner and significantly inhibits bone resorption induced by the canine adenocarcinoma model of humoral hypercalcemia of malignancy.
AuthorsT J Rosol, C C Capen
JournalEndocrinology (Endocrinology) Vol. 122 Issue 5 Pg. 2098-102 (May 1988) ISSN: 0013-7227 [Print] United States
PMID2834184 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Parathyroid Hormone
  • Peptide Fragments
  • Receptors, Cell Surface
  • Receptors, Parathyroid Hormone
  • Tissue Extracts
  • Teriparatide
  • parathyroid hormone (3-34)
  • parathyroid hormone (3-34) amide, Nle(8,18)-Nle(34)-
Topics
  • Adenocarcinoma (physiopathology, veterinary)
  • Animals
  • Animals, Newborn
  • Bone Resorption (drug effects)
  • Cell Line
  • Dog Diseases (physiopathology)
  • Dogs
  • Hypercalcemia (physiopathology, veterinary)
  • Mice
  • Mice, Inbred Strains
  • Mice, Nude
  • Neoplasm Transplantation
  • Parathyroid Hormone (pharmacology)
  • Peptide Fragments (pharmacology)
  • Receptors, Cell Surface (drug effects)
  • Receptors, Parathyroid Hormone
  • Teriparatide
  • Tissue Extracts (pharmacology)
  • Transplantation, Heterologous

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