{"title":"猪冠状动脉对次氯酸的血管舒缩反应中嘌呤能信号的参与。","authors":"Ashwaq Baghdadi, William R Dunn, Vera Ralevic","doi":"10.1007/s11302-025-10086-7","DOIUrl":null,"url":null,"abstract":"<p><p>Hypochlorous acid (HOCl) is generated by neutrophils during the innate immune response. ATP is released from cells by various stimuli and during inflammation but whether ATP is released by and participates in the response to HOCl is unclear. This study investigated vasomotor effects of HOCl on the porcine coronary artery (PCA) and the involvement of ATP and purine receptors. HOCl at 100 μM induced rapid and transient endothelium-dependent relaxation followed by slow and sustained endothelium-independent relaxation. Transient endothelium-dependent relaxation was induced by 500 μM HOCl, followed by endothelium-dependent contraction, then slow endothelium-independent relaxation. 8-(p-sulphophenyl)theophylline (8-SPT), an adenosine/P1 receptor antagonist, blocked rapid relaxation and contraction to HOCl but an A<sub>2A</sub> receptor antagonist, ZM 241385, and an A<sub>1</sub> receptor antagonist, DPCPX, had no effect. Suramin, a P2 receptor antagonist (and membrane channel inhibitor), blocked rapid relaxation (at 100 μM HOCl) and contraction to HOCl. Other antagonists for P2, P2X1, P2Y1 and P2X4 receptors (PPADS, reactive blue 2, NF449, MRS2179 and BX430) did not affect HOCl responses. Relaxation to exogenous ATP was inhibited by 8-SPT but not by suramin suggesting that suramin block of HOCl responses may involve inhibition of membrane channels and endogenous ATP release. Apyrase, which hydrolyzes nucleotides, abolished responses to HOCl, ATP and unexpectedly adenosine. Neither probenecid nor carbenoxelone (connexin and pannexin channel inhibitors) blocked responses to HOCl. Luminescent ATP assay showed that HOCl elicited ATP release from cultures of human coronary artery endothelial cells. These findings advance our understanding of inflammation by showing that HOCl evokes endothelium-dependent vasorelaxation and contraction in coronary arteries which may involve P1 receptors implicating endogenous adenosine, possibly generated from rapid metabolism of ATP released by HOCl.</p>","PeriodicalId":20952,"journal":{"name":"Purinergic Signalling","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery.\",\"authors\":\"Ashwaq Baghdadi, William R Dunn, Vera Ralevic\",\"doi\":\"10.1007/s11302-025-10086-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Hypochlorous acid (HOCl) is generated by neutrophils during the innate immune response. ATP is released from cells by various stimuli and during inflammation but whether ATP is released by and participates in the response to HOCl is unclear. This study investigated vasomotor effects of HOCl on the porcine coronary artery (PCA) and the involvement of ATP and purine receptors. HOCl at 100 μM induced rapid and transient endothelium-dependent relaxation followed by slow and sustained endothelium-independent relaxation. Transient endothelium-dependent relaxation was induced by 500 μM HOCl, followed by endothelium-dependent contraction, then slow endothelium-independent relaxation. 8-(p-sulphophenyl)theophylline (8-SPT), an adenosine/P1 receptor antagonist, blocked rapid relaxation and contraction to HOCl but an A<sub>2A</sub> receptor antagonist, ZM 241385, and an A<sub>1</sub> receptor antagonist, DPCPX, had no effect. Suramin, a P2 receptor antagonist (and membrane channel inhibitor), blocked rapid relaxation (at 100 μM HOCl) and contraction to HOCl. Other antagonists for P2, P2X1, P2Y1 and P2X4 receptors (PPADS, reactive blue 2, NF449, MRS2179 and BX430) did not affect HOCl responses. Relaxation to exogenous ATP was inhibited by 8-SPT but not by suramin suggesting that suramin block of HOCl responses may involve inhibition of membrane channels and endogenous ATP release. Apyrase, which hydrolyzes nucleotides, abolished responses to HOCl, ATP and unexpectedly adenosine. Neither probenecid nor carbenoxelone (connexin and pannexin channel inhibitors) blocked responses to HOCl. Luminescent ATP assay showed that HOCl elicited ATP release from cultures of human coronary artery endothelial cells. These findings advance our understanding of inflammation by showing that HOCl evokes endothelium-dependent vasorelaxation and contraction in coronary arteries which may involve P1 receptors implicating endogenous adenosine, possibly generated from rapid metabolism of ATP released by HOCl.</p>\",\"PeriodicalId\":20952,\"journal\":{\"name\":\"Purinergic Signalling\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2025-04-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Purinergic Signalling\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11302-025-10086-7\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Purinergic Signalling","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11302-025-10086-7","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Involvement of purinergic signalling in the vasomotor response to hypochlorous acid in porcine coronary artery.
Hypochlorous acid (HOCl) is generated by neutrophils during the innate immune response. ATP is released from cells by various stimuli and during inflammation but whether ATP is released by and participates in the response to HOCl is unclear. This study investigated vasomotor effects of HOCl on the porcine coronary artery (PCA) and the involvement of ATP and purine receptors. HOCl at 100 μM induced rapid and transient endothelium-dependent relaxation followed by slow and sustained endothelium-independent relaxation. Transient endothelium-dependent relaxation was induced by 500 μM HOCl, followed by endothelium-dependent contraction, then slow endothelium-independent relaxation. 8-(p-sulphophenyl)theophylline (8-SPT), an adenosine/P1 receptor antagonist, blocked rapid relaxation and contraction to HOCl but an A2A receptor antagonist, ZM 241385, and an A1 receptor antagonist, DPCPX, had no effect. Suramin, a P2 receptor antagonist (and membrane channel inhibitor), blocked rapid relaxation (at 100 μM HOCl) and contraction to HOCl. Other antagonists for P2, P2X1, P2Y1 and P2X4 receptors (PPADS, reactive blue 2, NF449, MRS2179 and BX430) did not affect HOCl responses. Relaxation to exogenous ATP was inhibited by 8-SPT but not by suramin suggesting that suramin block of HOCl responses may involve inhibition of membrane channels and endogenous ATP release. Apyrase, which hydrolyzes nucleotides, abolished responses to HOCl, ATP and unexpectedly adenosine. Neither probenecid nor carbenoxelone (connexin and pannexin channel inhibitors) blocked responses to HOCl. Luminescent ATP assay showed that HOCl elicited ATP release from cultures of human coronary artery endothelial cells. These findings advance our understanding of inflammation by showing that HOCl evokes endothelium-dependent vasorelaxation and contraction in coronary arteries which may involve P1 receptors implicating endogenous adenosine, possibly generated from rapid metabolism of ATP released by HOCl.
期刊介绍：
Nucleotides and nucleosides are primitive biological molecules that were utilized early in evolution both as intracellular energy sources and as extracellular signalling molecules. ATP was first identified as a neurotransmitter and later as a co-transmitter with all the established neurotransmitters in both peripheral and central nervous systems. Four subtypes of P1 (adenosine) receptors, 7 subtypes of P2X ion channel receptors and 8 subtypes of P2Y G protein-coupled receptors have currently been identified. Since P2 receptors were first cloned in the early 1990’s, there is clear evidence for the widespread distribution of both P1 and P2 receptor subtypes in neuronal and non-neuronal cells, including glial, immune, bone, muscle, endothelial, epithelial and endocrine cells.
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