在兔离体主动脉和隐动脉中，NF023可选择性拮抗通过P2X受体介导的血管收缩反应。

Vasoconstrictor responses via P2X-receptors are selectively antagonized by NF023 in rabbit isolated aorta and saphenous artery.

作者信息

Ziyal R, Ziganshin A U, Nickel P, Ardanuy U, Mutschler E, Lambrecht G, Burnstock G

机构信息

Department of Anatomy and Development Biology, University College London.

出版信息

Br J Pharmacol. 1997 Mar;120(5):954-60. doi: 10.1038/sj.bjp.0700984.

DOI:10.1038/sj.bjp.0700984

PMID:9138704

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1564544/

Abstract

The effects of NF023, the symmetrical 3'-urea of 8-(benzamido)naphthalene-1,3,5-trisulphonic acid), and its parent compound suramin were investigated on vasoconstrictor responses to alpha, beta-methylene ATP in rabbit isolated saphenous artery and vasodilator responses to ATP in noradrenaline-precontracted rabbit isolated thoracic aorta. 2. In rabbit isolated saphenous artery, alpha, beta-methylene ATP-induced vasoconstrictor responses via P2X-receptors were concentration-dependently and competitively antagonised by NF023 (30-300 microM; pA2 = 5.69 +/- 0.04). Suramin (100-1000 microM) also competitively blocked vasoconstrictor responses to alpha, beta-methylene ATP, albeit with lower potency (pA2 = 4.79 +/- 0.05). In contrast, NF023 (100 microM) did not significantly affect contractile responses to noradrenaline or histamine in the saphenous artery. 3. In noradrenaline-precontracted rabbit isolated thoracic aorta preparations, ATP (3-3000 microM) concentration-dependently induced relaxations via endothelium-dependent or smooth muscle P2Y-receptor subtypes. NF023 (30-300 microM) failed to block relaxant responses to ATP at endothelium-dependent P2Y-receptors, whereas suramin (100-1000 microM) did antagonise endothelium-dependent vasodilator responses to ATP. Neither NF023 (100 microM) nor suramin (300 microM) influenced vasorelaxant responses to ATP via endothelium-independent P2Y-receptors. 4. In conclusion, this study outlines the selectivity of NF023 as an effective P2X-receptor antagonist in rabbit isolated blood vessels without affecting endothelium-dependent or endothelium-independent P2Y-receptor subtypes, adrenoceptors or histamine receptors.

摘要

研究了NF023（8-（苯甲酰胺基）萘-1,3,5-三磺酸的对称3'-脲）及其母体化合物苏拉明对兔离体隐静脉中α,β-亚甲基ATP引起的血管收缩反应以及对去甲肾上腺素预收缩的兔离体胸主动脉中ATP引起的血管舒张反应的影响。2. 在兔离体隐静脉中，NF023（30 - 300μM；pA2 = 5.69±0.04）浓度依赖性且竞争性地拮抗了α,β-亚甲基ATP通过P2X受体诱导的血管收缩反应。苏拉明（100 - 1000μM）也竞争性地阻断了对α,β-亚甲基ATP的血管收缩反应，尽管效力较低（pA2 = 4.79±0.05）。相比之下，NF023（100μM）对隐静脉中去甲肾上腺素或组胺引起的收缩反应没有显著影响。3. 在去甲肾上腺素预收缩的兔离体胸主动脉标本中，ATP（3 - 3000μM）通过内皮依赖性或平滑肌P2Y受体亚型浓度依赖性地诱导舒张。NF023（30 - 300μM）未能阻断对内皮依赖性P2Y受体的ATP舒张反应，而苏拉明（100 - 1000μM）确实拮抗了对ATP的内皮依赖性血管舒张反应。NF023（100μM）和苏拉明（300μM）均未影响通过非内皮依赖性P2Y受体对ATP的血管舒张反应。4. 总之，本研究概述了NF023作为兔离体血管中一种有效的P