Effects of synthetic analogs and fragments of bovine parathyroid hormone on adenosine 3',5'-monophosphate level, ornithine decarboxylase activity, and glycosaminoglycan synthesis in rabbit costal chondrocytes in culture: Structure-activity relations

T. Takano, Masaharu Takigawa, E. Shirai, F. Suzuki, M. Rosenblatt

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Previously, we demonstrated that PTH increases the level of cAMP, the activity of ornithine decarboxylase (ODC; EC 4.1.1.17; which is a rate-limiting enzyme in polyamine biosynthesis), and glycosaminoglycan (GAG) synthesis (which is characteristic of the chondrocyte phenotype) in rabbit costal chondrocytes in culture. These studies suggested that the accumulation of cAMP and the induction of ODC by PTH are good markers of the differentiated phenotype of cultured chondrocytes. In the present study, the biological effects of a series of bovine PTH (bPTH) fragments and analogs on these three parameters of PTH action were examined. bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide and bPTH-(1-27) amide increased cAMP levels, ODC activity, and GAG synthesis in a dose-dependent manner over the concentration range of 10-9-10-5 M. The order of decreasing potency was: bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide, and bPTH-(1-27) amide. On the other hand, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide failed to increase cAMP levels, ODC activity, or GAG synthesis when present in concentrations up to 10-5 M. However, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide inhibited bPTH-(1-34)-stimulated increases in cAMP and ODC activity. These results partially define the principal structural determinants within the PTH molecule required for biological activity and expression of the differentiated phenotype of chondrocytes.

Original languageEnglish
Pages (from-to)2536-2542
Number of pages7
JournalEndocrinology
Volume116
Issue number6
Publication statusPublished - 1985
Externally publishedYes

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Ornithine Decarboxylase
Chondrocytes
Glycosaminoglycans
Adenosine
Rabbits
Amides
Parathyroid Hormone
bovine parathyroid hormone
Phenotype
Polyamines

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{2467d0fa15d84b13b4e249cb53515b46,
title = "Effects of synthetic analogs and fragments of bovine parathyroid hormone on adenosine 3',5'-monophosphate level, ornithine decarboxylase activity, and glycosaminoglycan synthesis in rabbit costal chondrocytes in culture: Structure-activity relations",
abstract = "Previously, we demonstrated that PTH increases the level of cAMP, the activity of ornithine decarboxylase (ODC; EC 4.1.1.17; which is a rate-limiting enzyme in polyamine biosynthesis), and glycosaminoglycan (GAG) synthesis (which is characteristic of the chondrocyte phenotype) in rabbit costal chondrocytes in culture. These studies suggested that the accumulation of cAMP and the induction of ODC by PTH are good markers of the differentiated phenotype of cultured chondrocytes. In the present study, the biological effects of a series of bovine PTH (bPTH) fragments and analogs on these three parameters of PTH action were examined. bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide and bPTH-(1-27) amide increased cAMP levels, ODC activity, and GAG synthesis in a dose-dependent manner over the concentration range of 10-9-10-5 M. The order of decreasing potency was: bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide, and bPTH-(1-27) amide. On the other hand, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide failed to increase cAMP levels, ODC activity, or GAG synthesis when present in concentrations up to 10-5 M. However, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide inhibited bPTH-(1-34)-stimulated increases in cAMP and ODC activity. These results partially define the principal structural determinants within the PTH molecule required for biological activity and expression of the differentiated phenotype of chondrocytes.",
author = "T. Takano and Masaharu Takigawa and E. Shirai and F. Suzuki and M. Rosenblatt",
year = "1985",
language = "English",
volume = "116",
pages = "2536--2542",
journal = "Endocrinology",
issn = "0013-7227",
publisher = "The Endocrine Society",
number = "6",

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TY - JOUR

T1 - Effects of synthetic analogs and fragments of bovine parathyroid hormone on adenosine 3',5'-monophosphate level, ornithine decarboxylase activity, and glycosaminoglycan synthesis in rabbit costal chondrocytes in culture

T2 - Structure-activity relations

AU - Takano, T.

AU - Takigawa, Masaharu

AU - Shirai, E.

AU - Suzuki, F.

AU - Rosenblatt, M.

PY - 1985

Y1 - 1985

N2 - Previously, we demonstrated that PTH increases the level of cAMP, the activity of ornithine decarboxylase (ODC; EC 4.1.1.17; which is a rate-limiting enzyme in polyamine biosynthesis), and glycosaminoglycan (GAG) synthesis (which is characteristic of the chondrocyte phenotype) in rabbit costal chondrocytes in culture. These studies suggested that the accumulation of cAMP and the induction of ODC by PTH are good markers of the differentiated phenotype of cultured chondrocytes. In the present study, the biological effects of a series of bovine PTH (bPTH) fragments and analogs on these three parameters of PTH action were examined. bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide and bPTH-(1-27) amide increased cAMP levels, ODC activity, and GAG synthesis in a dose-dependent manner over the concentration range of 10-9-10-5 M. The order of decreasing potency was: bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide, and bPTH-(1-27) amide. On the other hand, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide failed to increase cAMP levels, ODC activity, or GAG synthesis when present in concentrations up to 10-5 M. However, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide inhibited bPTH-(1-34)-stimulated increases in cAMP and ODC activity. These results partially define the principal structural determinants within the PTH molecule required for biological activity and expression of the differentiated phenotype of chondrocytes.

AB - Previously, we demonstrated that PTH increases the level of cAMP, the activity of ornithine decarboxylase (ODC; EC 4.1.1.17; which is a rate-limiting enzyme in polyamine biosynthesis), and glycosaminoglycan (GAG) synthesis (which is characteristic of the chondrocyte phenotype) in rabbit costal chondrocytes in culture. These studies suggested that the accumulation of cAMP and the induction of ODC by PTH are good markers of the differentiated phenotype of cultured chondrocytes. In the present study, the biological effects of a series of bovine PTH (bPTH) fragments and analogs on these three parameters of PTH action were examined. bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide and bPTH-(1-27) amide increased cAMP levels, ODC activity, and GAG synthesis in a dose-dependent manner over the concentration range of 10-9-10-5 M. The order of decreasing potency was: bPTH-(1-34),[Nle8,Nle18,Tyr34]bPTH-(1-34) amide, and bPTH-(1-27) amide. On the other hand, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide failed to increase cAMP levels, ODC activity, or GAG synthesis when present in concentrations up to 10-5 M. However, [Nle8,Nle18,Tyr34]bPTH-(3-34) amide, bPTH-(5-27) amide, and [Tyr34]bPTH-(20-34) amide inhibited bPTH-(1-34)-stimulated increases in cAMP and ODC activity. These results partially define the principal structural determinants within the PTH molecule required for biological activity and expression of the differentiated phenotype of chondrocytes.

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