ATP is not involved in α₁-adrenoceptor-mediated vasoconstriction in resistance arteries

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• 作者：James A. Angus ; ^{jamesaa@unimelb.edu.au" class="auth_mail" title="E-mail the corresponding author} ; Christine E. Wright ^{cewright@unimelb.edu.au" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ATP ; adenosine triphosphate ; Emax ; maximum possible effect for the agonist ; KPSS ; isotonic potassium physiological salt solution ; NF449 octasodium salt ; 4 ; 4&prime ; 4&Prime ; 4‴-[carbonylbis[imino-5 ; 1 ; 3-benzenetriylbis(carbonylimino)]] tetrakis-1 ; 3-benzenedisulfonic acid ; octasodium salt ; PSS ; physiological salt solution
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：15 December 2015
• 年：2015
• 卷：769
• 期：Complete
• 页码：162-166
• 全文大小：476 K

文摘

Recent publications suggest that α₁-adrenoceptor stimulation by exogenous agonists such as phenylephrine in resistance arteries cause contraction through the release of ATP from within the vascular smooth muscle cells. This ATP exits the cell through pannexin-1 channels to act back “autocrine-like” on P2 receptors on the smooth muscle that cause the contraction. In this work we directly test this hypothesis by using a selective P2X₁ purinoceptor antagonist NF449 (1–10 µM) against phenylephrine and ATP concentration–response curves in small mesenteric arteries of the rat and thoracodorsal arteries of the mouse. We show that NF449 is a simple competitive antagonist of ATP with a pK_B of 6.43 and 6.41 in rat and mouse arteries, respectively, but did not antagonise phenylephrine concentration–response curves. This work cautions against the growing overstated role of the reputed pannexin-1/ATP release axis following α₁-adrenoceptor activation in small resistance arteries.