Nicotine’s impact on platelet function: insights into hemostasis mechanisms
IntroductionTraditional 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.Methods and Resul...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-01-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2024.1512142/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832593721641664512 |
|---|---|
| author | Xiayu Wu Xiayu Wu Yongjun Liu Changhao Zou Changhao Zou Fuqin He Fuqin He Fang Guo Fang Guo Sijia Liu Sijia Liu Yi Fan Yi Fan Xuedong Zhu Xuedong Zhu Qianyi Zhou Qianyi Zhou Dan Shu Dan Shu |
| author_facet | Xiayu Wu Xiayu Wu Yongjun Liu Changhao Zou Changhao Zou Fuqin He Fuqin He Fang Guo Fang Guo Sijia Liu Sijia Liu Yi Fan Yi Fan Xuedong Zhu Xuedong Zhu Qianyi Zhou Qianyi Zhou Dan Shu Dan Shu |
| author_sort | Xiayu Wu |
| collection | DOAJ |
| description | IntroductionTraditional 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.Methods and ResultsThis 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.DiscussionIn 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. |
| format | Article |
| id | doaj-art-29021f256a5c4043b1b93987a49f334d |
| institution | Kabale University |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-29021f256a5c4043b1b93987a49f334d2025-01-20T09:30:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-01-011510.3389/fphar.2024.15121421512142Nicotine’s impact on platelet function: insights into hemostasis mechanismsXiayu Wu0Xiayu Wu1Yongjun Liu2Changhao Zou3Changhao Zou4Fuqin He5Fuqin He6Fang Guo7Fang Guo8Sijia Liu9Sijia Liu10Yi Fan11Yi Fan12Xuedong Zhu13Xuedong Zhu14Qianyi Zhou15Qianyi Zhou16Dan Shu17Dan Shu18Institute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaHunan Tobacco Science Research Institute, Changsha, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Pharmaceutical Innovation, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaInstitute of Cardiovascular Diseases, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, ChinaIntroductionTraditional 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.Methods and ResultsThis 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.DiscussionIn 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.https://www.frontiersin.org/articles/10.3389/fphar.2024.1512142/fullnicotineplateletsthrombin[Ca2+]iPAR4 receptor pathwayαIIbβ3 |
| spellingShingle | Xiayu Wu Xiayu Wu Yongjun Liu Changhao Zou Changhao Zou Fuqin He Fuqin He Fang Guo Fang Guo Sijia Liu Sijia Liu Yi Fan Yi Fan Xuedong Zhu Xuedong Zhu Qianyi Zhou Qianyi Zhou Dan Shu Dan Shu Nicotine’s impact on platelet function: insights into hemostasis mechanisms Frontiers in Pharmacology nicotine platelets thrombin [Ca2+]i PAR4 receptor pathway αIIbβ3 |
| title | Nicotine’s impact on platelet function: insights into hemostasis mechanisms |
| title_full | Nicotine’s impact on platelet function: insights into hemostasis mechanisms |
| title_fullStr | Nicotine’s impact on platelet function: insights into hemostasis mechanisms |
| title_full_unstemmed | Nicotine’s impact on platelet function: insights into hemostasis mechanisms |
| title_short | Nicotine’s impact on platelet function: insights into hemostasis mechanisms |
| title_sort | nicotine s impact on platelet function insights into hemostasis mechanisms |
| topic | nicotine platelets thrombin [Ca2+]i PAR4 receptor pathway αIIbβ3 |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2024.1512142/full |
| work_keys_str_mv | AT xiayuwu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT xiayuwu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT yongjunliu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT changhaozou nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT changhaozou nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT fuqinhe nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT fuqinhe nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT fangguo nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT fangguo nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT sijialiu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT sijialiu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT yifan nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT yifan nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT xuedongzhu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT xuedongzhu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT qianyizhou nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT qianyizhou nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT danshu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms AT danshu nicotinesimpactonplateletfunctioninsightsintohemostasismechanisms |