UND Life Sciences, Battle Ground, WA 98604, USA.
Department of Biotechnology, Indian Institute of Technology-Hyderabad, 502285 Telangana, India.
Discov Med. 2023 Aug;35(177):451-457. doi: 10.24976/Discov.Med.202335177.46.
Seasonal variation in blood pressure that is higher in winter and lower in summer has been attributed to several factors that include changes in the activity of autonomic nervous system, vasopressin and expression of endothelial nitric oxide synthase (eNOS). Transient receptor potential melastatin 8 (TRPM8), a non-selective Ca-permeable cationic channel, serves as a molecular transducer to sense cold by the somatosensory system. TRPM8 is sensitive to protein kinase C (PKC) and phosphatidyl inositol-4,5-biphosphate [PI(4,5)P] suggesting that TRPM8 is stimulated by phospholipase C (PLC)-coupled receptors. Activated PLC inhibits TRPM8 by reducing cellular PI(4,5)P levels and by activating PKC via diacyl glycerol. Bradykinin and prostaglandin E2 (PGE2), which are pro-inflammatory molecules, reduce the responses to cold, suggesting that phospholipase A2 (PLA2), which releases polyunsaturated fatty acids (PUFAs), the precursors of various eicosanoids, from the cell membrane lipid pool can modulate the function of TRPM8. TRPM8 functions as a nociceptor and modulates immune response. These and other studies indicate that cold-induced activation of transient receptor potential melastatin 8 (TRPM8) plays a role in the pathobiology of hypertension, preeclampsia and in the regulation of inflammation and immunity.
血压的季节性变化表现为冬季升高、夏季降低，其原因涉及多种因素，包括自主神经系统、血管加压素和内皮型一氧化氮合酶（eNOS）活性的改变。瞬时受体电位阳离子通道亚家族 M 成员 8（TRPM8）是一种非选择性钙通透性阳离子通道，作为感觉系统感知寒冷的分子转导器。TRPM8 对蛋白激酶 C（PKC）和磷脂酰肌醇-4,5-二磷酸[PI（4,5）P]敏感，表明 TRPM8 受磷酯酶 C（PLC）偶联受体的刺激。激活的 PLC 通过降低细胞内 PI（4,5）P 水平和通过二酰基甘油激活 PKC 来抑制 TRPM8。具有促炎作用的缓激肽和前列腺素 E2（PGE2）可降低对寒冷的反应，这表明可从细胞膜脂质池中释放多不饱和脂肪酸（PUFAs），即各种类花生酸的前体的磷脂酶 A2（PLA2），可调节 TRPM8 的功能。TRPM8 作为伤害感受器发挥作用，并调节免疫反应。这些和其他研究表明，冷诱导的瞬时受体电位阳离子通道亚家族 M 成员 8（TRPM8）的激活在高血压、先兆子痫的病理生物学以及炎症和免疫调节中发挥作用。
