In vitro and in vivo antagonists against parathyroid hormone-related protein

K Nagasaki; K Yamaguchi; Y Miyake; C Hayashi; S Honda; K Urakami; K Miki; S Kimura; T Watanabe; K Abe

doi:10.1016/0006-291x(89)92826-x

In vitro and in vivo antagonists against parathyroid hormone-related protein

Biochem Biophys Res Commun. 1989 Feb 15;158(3):1036-42. doi: 10.1016/0006-291x(89)92826-x.

Authors

K Nagasaki¹, K Yamaguchi, Y Miyake, C Hayashi, S Honda, K Urakami, K Miki, S Kimura, T Watanabe, K Abe, et al.

Affiliation

¹ Growth Factor Division, National Cancer Center Research Institute, Tokyo, Japan.

PMID: 2537630
DOI: 10.1016/0006-291x(89)92826-x

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.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adenylyl Cyclases / metabolism
Animals
Calcium / blood
Cyclic AMP / biosynthesis
Humans
Mice
Mice, Nude
Neoplasm Proteins / antagonists & inhibitors*
Neoplasm Proteins / metabolism
Neoplasm Proteins / pharmacology
Osteosarcoma / metabolism
Parathyroid Hormone
Parathyroid Hormone-Related Protein
Peptide Fragments / pharmacology
Proteins*
Rats
Tumor Cells, Cultured

Substances

Neoplasm Proteins
PTHLH protein, human
Parathyroid Hormone
Parathyroid Hormone-Related Protein
Peptide Fragments
Proteins
parathyroid hormone-related protein (1-34)
Cyclic AMP
Adenylyl Cyclases
Calcium