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CC BY 4.0 · TH Open 2017; 01(02): e122-e129
DOI: 10.1055/s-0037-1607979
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Cigarette Smoke Extract Inhibits Platelet Aggregation by Suppressing Cyclooxygenase Activity

Hitoshi Kashiwagi
1   Department of Pharmacology, Asahikawa Medical University, Asahikawa, Japan
2   Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan
,
Koh-ichi Yuhki
1   Department of Pharmacology, Asahikawa Medical University, Asahikawa, Japan
2   Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan
,
Yoshitaka Imamichi
1   Department of Pharmacology, Asahikawa Medical University, Asahikawa, Japan
,
Fumiaki Kojima
2   Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan
3   Department of Pharmacology, Kitasato University, Sagamihara, Japan
,
Shima Kumei
1   Department of Pharmacology, Asahikawa Medical University, Asahikawa, Japan
2   Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan
,
Tsunehito Higashi
4   Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
,
Takahiro Horinouchi
4   Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
,
Soichi Miwa
4   Department of Cellular Pharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan
,
Shuh Narumiya
2   Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan
5   Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto, Japan
,
Fumitaka Ushikubi
1   Department of Pharmacology, Asahikawa Medical University, Asahikawa, Japan
2   Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Tokyo, Japan
› Author Affiliations
Further Information

Publication History

25 August 2017

19 September 2017

Publication Date:
30 October 2017 (online)

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Abstract

The results of studies that were performed to determine whether cigarette smoking affects platelet function have been controversial, and the effects of nicotine- and tar-free cigarette smoke extract (CSE) on platelet function remain to be determined. The aim of this study was to determine the effect of CSE on platelet aggregation and to clarify the mechanism by which CSE affects platelet function. CSE inhibited murine platelet aggregation induced by 9,11-dideoxy-9α,11α-methanoepoxy-prosta-5Z,13E-dien-1-oic acid (U-46619), a thromboxane (TX) A2 receptor agonist, and that induced by collagen with respective IC50 values of 1.05 ± 0.14% and 1.34 ± 0.19%. A similar inhibitory action of CSE was also observed in human platelets. CSE inhibited arachidonic acid–induced TXA2 production in murine platelets with an IC50 value of 7.32 ± 2.00%. Accordingly, the inhibitory effect of CSE on collagen-induced aggregation was significantly blunted in platelets lacking the TXA2 receptor compared with the inhibitory effect in control platelets. In contrast, the antiplatelet effects of CSE in platelets lacking each inhibitory prostanoid receptor, prostaglandin (PG) I2 receptor and PGE2 receptor subtypes EP2 and EP4, were not significantly different from the effects in respective control platelets. Among the enzymes responsible for TXA2 production in platelets, the activity of cyclooxygenase (COX)-1 was inhibited by CSE with an IC50 value of 1.07 ± 0.15% in an uncompetitive manner. In contrast, the activity of TX synthase was enhanced by CSE. The results indicate that CSE inhibits COX-1 activity and thereby decreases TXA2 production in platelets, leading to inhibition of platelet aggregation.

Keywords

cigarette smoke extract - platelets - thromboxane A2 - cyclooxygenase

Grants or Other Financial Support

This work was supported by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science and by a grant from Core Research for Evolutional Science and Technology (CREST) of the Japan Science and Technology Agency (JST). This work was also supported by a grant from the Smoking Research Foundation, but the foundation played no role in research design, conduct of experiments, data analysis, and preparation of the manuscript.


 

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