title: ATP is not involved in α1-adrenoceptor-mediated vasoconstriction in resistance arteries.
abstract: 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 (1-10µM) 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 pKB 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.
authors.affiliation: Cardiovascular Therapeutics Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Victoria 3010, Australia. Electronic address: jamesaa@unimelb.edu.au.
authors.forename: James A
authors.initials: JA
authors.lastname: Angus
authors.affiliation: Cardiovascular Therapeutics Unit, Department of Pharmacology and Therapeutics, University of Melbourne, Victoria 3010, Australia. Electronic address: cewright@unimelb.edu.au.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wright
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D064131:Back Muscles / Q000098:blood supply; D001557:Benzenesulfonates / Q000494:pharmacology; D017630:Connexins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: C110258:4,4,',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis(carbonylimino)))tetrakis(benzene-1,3-disulfonate); D001557:Benzenesulfonates; D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine; D000255:Adenosine Triphosphate
keywords: ATP release; Adenosine triphosphate (PubChem CID: 5957); NF449; NF449 octasodium salt (PubChem CID: 6093161); P2X(1) receptors; Pannexin-1 channels; Phenylephrine; Phenylephrine hydrochloride (PubChem CID: 5284443); Vascular contraction; α(1)-adrenoceptors