Inhibition of in vitro bone resorption by a parathyroid hormone receptor antagonist in the canine adenocarcinoma model of humoral hypercalcemia of malignancy.
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.
Rosol
T J
TJ
Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.
Capen
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CC
D000230:Adenocarcinoma / Q000503:physiopathology / Q000662:veterinary*; D000818:Animals; D000831:Animals, Newborn; D001862:Bone Resorption / Q000187:drug effects*; D002460:Cell Line; D004283:Dog Diseases / Q000503:physiopathology*; D004285:Dogs; D006934:Hypercalcemia / Q000503:physiopathology / Q000662:veterinary*; D051379:Mice; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D018016:Receptors, Parathyroid Hormone; D019379:Teriparatide; D014020:Tissue Extracts / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018016:Receptors, Parathyroid Hormone; D014020:Tissue Extracts; D019379:Teriparatide; C031617:parathyroid hormone (3-34); C025497:parathyroid hormone (3-34) amide, Nle(8,18)-Nle(34)-