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P2X receptors and bioactive lipids interact to modulate inflammation.
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DOI：10.1016/j.jlr.2026.101084.png)
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Abstract
En 中文
P2X receptors are purinergic receptors activated in the presence of extracellular ATP. These receptors are involved in the pathogenesis of various diseases, including inflammatory diseases, and are also associated with pain. These ionotropic receptors are activated when ATP is released during the inflammatory process. This can occur because, during the inflammatory process, phospholipase A2 is activated, releasing arachidonic acid, which is converted by COX-1 and COX-2 into prostaglandins or thromboxanes. In this context, prostaglandins sensitize cells, leading them to release ATP, which binds to P2X receptors, thereby activating their ion channels. These channels can act in various ways: P2X4 is involved in neuropathic pain, whereas P2X7 receptors can activate the NLRP3 inflammasome, which, in turn, induces IL-1β release and activates the COX pathway, generating an inflammatory cycle. In addition to prostaglandins, other bioactive lipids are also associated with increased expression of P2X receptors, such as leukotrienes and thromboxanes, which can increase Ca2+ influx, facilitating the release of extracellular ATP. Bioactive lipids, such as resolvins, lipoxins, maresins, and protectins, which have anti-inflammatory effects and promote homeostasis, can attenuate inflammation. They act indirectly on P2X receptors by controlling the inflammatory process, thereby decreasing ATP release and lowering P2X receptor expression. There are also lipids that structurally assist in P2X receptor activity, such as cholesterol and ceramides. Ceramides also play a role in the cell signaling process, inducing apoptosis. This review sought to elucidate how bioactive lipids regulate P2X receptor expression.
Keywords:
P2X receptor
bioactive lipids
ATP
inflammation
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