title: In vitro and in vivo antagonists against parathyroid hormone-related protein.
abstract: Four analogues of parathyroid hormone-related protein (PTHrP), PTHrP(7-34)NH2, (10-34)NH2, (15-34)NH2 and (20-34)NH2, were synthesized and their antagonistic activity against PTHrP(1-34) was examined in vitro and in vivo. In vitro studies revealed that all four analogues antagonized PTHrP-stimulated cyclic AMP production in rat osteosarcoma cells (ROS 17/2.8), and that PTHrP(7-34)NH2 and PTHrP(10-34)NH2 had potent antagonistic activity. In vivo experiments in nude mice also revealed that PTHrP(7-34)NH2 completely inhibited hypercalcemia induced by PTHrP(1-34), indicating that these analogues antagonize the effects of PTHrP(1-34) in vitro and in vivo.
authors.affiliation: Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Nagasaki
authors.forename: K
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Y
authors.initials: Y
authors.lastname: Miyake
authors.forename: C
authors.initials: C
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Honda
authors.forename: K
authors.initials: K
authors.lastname: Urakami
authors.forename: K
authors.initials: K
authors.lastname: Miki
authors.forename: S
authors.initials: S
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Abe
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D012516:Osteosarcoma / Q000378:metabolism; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D011506:Proteins; D051381:Rats; D014407:Tumor Cells, Cultured
chemical_list: D009363:Neoplasm Proteins; C470121:PTHLH protein, human; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; C054296:parathyroid hormone-related protein (1-34); D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D002118:Calcium