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Title: U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells

Abstract

The effects of U-61,431F, ciprostene, a stable prostacyclin analogue, were examined on the proliferation of cultured quiescent bovine aortic endothelial cells (EC) and smooth muscle cells (SMC). After stimulation with 5% fetal calf serum, U-61,431F suppressed both the DNA synthesis and proliferation of SMC dose-dependently at the concentration of 3-100 microM, but had no effect on either of them in EC at a concentration of up to 30 microM. The inhibitory effect on DNA synthesis was greater in SMC than in EC at 3-50 microM. When SMC were stimulated with platelet-derived growth factor (PDGF) for 2 hrs followed by a 22-hr incubation with insulin, U-61,431F (1-50 microM) administered at the time of PDGF stimulation did not inhibit DNA synthesis. SMC initiated and terminated DNA synthesis at about 15-18 h and 24 h after stimulation with serum, respectively. Inhibition of DNA synthesis in serum-stimulated SMC as a function of the addition time of U-61,431F reduced at 3-12 h after the stimulation. U-61,431F raised the cyclic AMP (cAMP) content in SMC. Moreover, a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and a more specific cAMP phosphodiesterase inhibitor, Ro 20-1724, augmented the inhibition of DNA synthesis in SMC concomitant with further elevation of cAMP level. These resultsmore » suggest that U-61,431F inhibits DNA synthesis of SMC acting in the progression stage rather than in the competence stage, with little antiproliferative effect on EC. cAMP may play an important role in its antiproliferative action in SMC.« less

Authors:
; ; ;  [1]
  1. Kyoto Univ., (Japan)
Publication Date:
OSTI Identifier:
5803158
Resource Type:
Journal Article
Journal Name:
Prostaglandins; (USA)
Additional Journal Information:
Journal Volume: 41:2; Journal ID: ISSN 0090-6980
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; ANIMAL CELLS; CELL PROLIFERATION; PROSTAGLANDINS; BIOCHEMICAL REACTION KINETICS; AMP; AORTA; CATTLE; DNA REPLICATION; DOSE-RESPONSE RELATIONSHIPS; ENDOTHELIUM; ENZYME INHIBITORS; GROWTH FACTORS; INHIBITION; INSULIN; MUSCLES; THYMIDINE; TRACER TECHNIQUES; TRITIUM COMPOUNDS; ANIMAL TISSUES; ANIMALS; ARTERIES; AZINES; BLOOD VESSELS; BODY; CARDIOVASCULAR SYSTEM; DOMESTIC ANIMALS; HETEROCYCLIC COMPOUNDS; HORMONES; HYDROGEN COMPOUNDS; ISOTOPE APPLICATIONS; KINETICS; MAMMALS; MITOGENS; NUCLEIC ACID REPLICATION; NUCLEOSIDES; NUCLEOTIDES; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PEPTIDE HORMONES; PROTEINS; PYRIMIDINES; REACTION KINETICS; RIBOSIDES; RUMINANTS; TISSUES; VERTEBRATES; 550201* - Biochemistry- Tracer Techniques

Citation Formats

Shirotani, M, Yui, Y, Hattori, R, and Kawai, C. U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells. United States: N. p., 1991. Web. doi:10.1016/0090-6980(91)90023-9.
Shirotani, M, Yui, Y, Hattori, R, & Kawai, C. U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells. United States. https://doi.org/10.1016/0090-6980(91)90023-9
Shirotani, M, Yui, Y, Hattori, R, and Kawai, C. 1991. "U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells". United States. https://doi.org/10.1016/0090-6980(91)90023-9.
@article{osti_5803158,
title = {U-61,431F, a stable prostacyclin analogue, inhibits the proliferation of bovine vascular smooth muscle cells with little antiproliferative effect on endothelial cells},
author = {Shirotani, M and Yui, Y and Hattori, R and Kawai, C},
abstractNote = {The effects of U-61,431F, ciprostene, a stable prostacyclin analogue, were examined on the proliferation of cultured quiescent bovine aortic endothelial cells (EC) and smooth muscle cells (SMC). After stimulation with 5% fetal calf serum, U-61,431F suppressed both the DNA synthesis and proliferation of SMC dose-dependently at the concentration of 3-100 microM, but had no effect on either of them in EC at a concentration of up to 30 microM. The inhibitory effect on DNA synthesis was greater in SMC than in EC at 3-50 microM. When SMC were stimulated with platelet-derived growth factor (PDGF) for 2 hrs followed by a 22-hr incubation with insulin, U-61,431F (1-50 microM) administered at the time of PDGF stimulation did not inhibit DNA synthesis. SMC initiated and terminated DNA synthesis at about 15-18 h and 24 h after stimulation with serum, respectively. Inhibition of DNA synthesis in serum-stimulated SMC as a function of the addition time of U-61,431F reduced at 3-12 h after the stimulation. U-61,431F raised the cyclic AMP (cAMP) content in SMC. Moreover, a phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, and a more specific cAMP phosphodiesterase inhibitor, Ro 20-1724, augmented the inhibition of DNA synthesis in SMC concomitant with further elevation of cAMP level. These results suggest that U-61,431F inhibits DNA synthesis of SMC acting in the progression stage rather than in the competence stage, with little antiproliferative effect on EC. cAMP may play an important role in its antiproliferative action in SMC.},
doi = {10.1016/0090-6980(91)90023-9},
url = {https://www.osti.gov/biblio/5803158}, journal = {Prostaglandins; (USA)},
issn = {0090-6980},
number = ,
volume = 41:2,
place = {United States},
year = {Fri Feb 01 00:00:00 EST 1991},
month = {Fri Feb 01 00:00:00 EST 1991}
}