Influence of Nicotine and Cotinine on the Expression of Plasminogen Activator Activity in Bovine Aortic Endothelial Cells

Be-Sheng Kuo; Maciej Dryjski; Thorir D Bjornsson

doi:10.1055/s-0038-1646529

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1989; 61(01): 070-076
DOI: 10.1055/s-0038-1646529

Original Article

Schattauer GmbH Stuttgart

Influence of Nicotine and Cotinine on the Expression of Plasminogen Activator Activity in Bovine Aortic Endothelial Cells

Authors

Be-Sheng Kuo

The Division of Clinical Pharmacology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA and the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Duke University Medical Center, Durham, NC, USA
Maciej Dryjski

The Division of Clinical Pharmacology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA and the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Duke University Medical Center, Durham, NC, USA
Thorir D Bjornsson

The Division of Clinical Pharmacology, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA and the Division of Clinical Pharmacology, Departments of Medicine and Pharmacology, Duke University Medical Center, Durham, NC, USA

Abstract

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Summary

The effects of nicotine and its major metabolite, cotinine, were evaluated on the secretion of plasminogen activator (PA) and plasminogen activator inhibitor (PAI) in cultured bovine aortic endothelial cells. Both compounds increased PA secretion, determined by ¹²⁵I-fibrin plate assay, in a time- and dose-dependent manner. Maximum effects after 24 hr incubation were observed for nicotine at 10^-8 M and for cotinine at 10^-7 M, which corresponded to about 2.6-fold increases over control for both compounds. The pharmacological PA stimulation required both RNA and protein syntheses, as evidenced by inhibition by acfinomycin D and cycloheximide. Both control and treated cells produced multiple forms of PA, as evaluated by SDS-PAGE zymography, and a single form of PAI, as evidenced by reverse fibrin autography. Although activities of all species of PA were enhanced by nicotine and cotinine, these compounds had no significant effects on the release of PAI. These results thus suggest that nicotine and cotinine may have fibrinolytic activity in vivo.

Key words

Plasminogen activator - Plasminogen activator inhibitor - Nicotine - Cotinine - Bovine aortic endothelial cells

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References

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