An Qimin, Yue Gengyu, Yang Xiaoxu, Lou Jun, Shan Weixi, Ding Jianhong, Jin Zhe, Hu Yanxia, Du Qian, Liao Qiushi, Xie Rui, Xu Jingyu
Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
The Collaborative Innovation Center of Tissue Damage Repair and Regeneration Medicine of Zunyi Medical University, Zunyi, China.
Front Physiol. 2021 Dec 24;12:781069. doi: 10.3389/fphys.2021.781069. eCollection 2021.
P2X receptors (P2XRs) are trimeric, non-selective cation channels activated by extracellular ATP and widely distributed in the digestive system. P2XRs have an important role in the physiological function of the digestive system, such as neurotransmission, ion transports, proliferation and apoptosis, muscle contraction, and relaxation. P2XRs can be involved in pain mechanisms both centrally and in the periphery and confirmed the association of P2XRs with visceral pain. In the periphery, ATP can be released as a result of tissue injury, visceral distension, or sympathetic activation and can excite nociceptive primary afferents by acting at homomeric P2X(3)R or heteromeric P2X(2/3)R. Thus, peripheral P2XRs, and homomeric P2X(3) and/or heteromeric P2X(2/3)R in particular, constitute attractive targets for analgesic drugs. Recently studies have shown that P2XRs have made significant advances in inflammation and cancer. P2X7R mediates NLRP3 inflammasome activation, cytokine and chemokine release, T lymphocyte survival and differentiation, transcription factor activation, and cell death. The P2X7R is a potent stimulant of inflammation and immunity and a promoter of cancer cell growth. This makes P2X7R an appealing target for anti-inflammatory and anti-cancer therapy. It is believed that with the further study of P2XRs and its subtypes, P2XRs and its specific antagonists will be expected to be widely used in the treatment of human digestive diseases in the future.
P2X受体（P2XRs）是三聚体非选择性阳离子通道，由细胞外ATP激活，广泛分布于消化系统。P2XRs在消化系统的生理功能中发挥重要作用，如神经传递、离子转运、增殖与凋亡、肌肉收缩和舒张。P2XRs可在中枢和外周参与疼痛机制，并证实了P2XRs与内脏痛的关联。在外周，ATP可因组织损伤、内脏扩张或交感神经激活而释放，并可通过作用于同聚体P2X(3)R或异聚体P2X(2/3)R来兴奋伤害性初级传入神经。因此，外周P2XRs，尤其是同聚体P2X(3)和/或异聚体P2X(2/3)R，构成了镇痛药的有吸引力的靶点。最近的研究表明，P2XRs在炎症和癌症方面取得了重大进展。P2X7R介导NLRP3炎性小体激活、细胞因子和趋化因子释放、T淋巴细胞存活和分化、转录因子激活以及细胞死亡。P2X7R是炎症和免疫的强效刺激剂以及癌细胞生长的促进剂。这使得P2X7R成为抗炎和抗癌治疗的一个有吸引力的靶点。相信随着对P2XRs及其亚型的进一步研究，P2XRs及其特异性拮抗剂有望在未来广泛应用于人类消化系统疾病的治疗。
