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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1512142

Nicotine's Impact on Platelet Function: Insights into Hemostasis Mechanisms

Provisionally accepted
Xiayu Wu Xiayu Wu 1Yongjun Liu Yongjun Liu 2Changhao Zou Changhao Zou 1Fuqin He Fuqin He 1Fang Guo Fang Guo 1Sijia Liu Sijia Liu 1Yi Fan Yi Fan 1Xuedong Zhu Xuedong Zhu 1Dan Shu Dan Shu 1*
  • 1 Wuhan University of Science and Technology, Wuhan, China
  • 2 Hunan Tobacco Science Research Institute, Changsha, China

The final, formatted version of the article will be published soon.

    Traditional Miao and Dai Chinese medicines have used nicotine-rich leaf tobacco to treat traumatic injuries by promoting hemostasis. While nicotine is known to enhance platelet aggregation, its effects on other platelet functions and underlying mechanisms remain unclear. This study aimed to thoroughly investigate nicotine's effects on human platelets and its pharmacological mechanisms, using thromboelastography to assess nicotine's impact on platelet function during coagulation. This study aimed to investigate the functional effects of nicotine on human platelets and elucidate its pharmacological mechanisms. The impact of nicotine on platelet function during the coagulation process was assessed using thromboelastography. Further studies showed that nicotine fully activates washed platelets, promoting aggregation, granule release, adhesion, spreading, and plaque retraction. Concurrently, nicotine was found to enhance the intracellular concentration of calcium ions in platelets ([Ca2+]i). To explore the underlying mechanisms, molecular docking software was employed to identify the platelet membrane receptors PAR1 and PAR4, which exhibited the highest docking scores with nicotine. Intervention with two receptor inhibitors demonstrated that only the PAR4 inhibitor could reverse the stimulatory effects of nicotine on platelet granule release. Through the examination of alterations in the downstream signaling pathways of PAR4 receptors, it was determined that nicotine promo-facilitates the phosphorylation of PI3K, AKT, and ERK1/2 proteins, subsequently contributing to the activation of αIIbβ3 receptors in platelets. Conversely, the application of PAR4 inhibitors was found to reverse these effects. In conclusion, nicotine activates αIIbβ3 receptors and significantly enhances platelet function by promoting the phosphorylation of the platelet PAR4 receptor signaling pathway. These findings suggest the potential utility of nicotine as a hemostatic agent.

    Keywords: Nicotine, platelets, Thrombin, [Ca 2+ ]i, PAR4 receptor pathway, αIIbβ3

    Received: 16 Oct 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Wu, Liu, Zou, He, Guo, Liu, Fan, Zhu and Shu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Dan Shu, Wuhan University of Science and Technology, Wuhan, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.