title: A2B adenosine receptor mediates human chorionic vasoconstriction and signals through arachidonic acid cascade.
abstract: Because adenosine is a vascular tone modulator, we examined the effect of adenosine and congeners in the vascular reactivity of isolated human placental vessels and in perfused cotyledons. We characterized its vasomotor action and tentatively identified the receptor subtypes and their intracellular signaling mechanisms. We recorded isometric tension from the circular layer of chorionic vessel rings maintained under 1.5 g of basal tension or precontracted with KCl. The relative order of potency of adenosine and structural analogs is consistent with the expression of A2B receptors, 5'-(N-ethylcarboxamido)adenosine (NECA) being the most potent. The maximal contraction ranged from 45% to 60% of the KCl standard response, except for an A2A receptor agonist that did not exceed 15%. Consistently, NECA was 100-fold more potent than adenosine to raise the perfusion pressure of ex vivo perfused cotyledons. In contrast, a selective A3 receptor agonist relaxed precontracted rings of chorionic vessels. Whereas a selective A3 receptor antagonist was ineffective to antagonize adenosine-induced contraction, A2 or A1 receptor antagonists reduced adenosine-induced vasoconstriction concentration-dependently. Denudation of the endothelial layer reduced adenosine- and NECA-induced contractions by 50-70%. Furthermore, indomethacin reduced adenosine- or NECA-induced contractions concentration-dependently in intact and endothelium-denuded rings. A thromboxane receptor antagonist blocked adenosine- and NECA-induced contractions in intact and endothelium-denuded rings, suggesting the involvement of an arachidonic acid metabolite as the mediator of the vasoconstriction. We propose that adenosine A2B receptors mediate the adenosine-induced contraction vasomotor effect in human chorionic vessels and that this involves synthesis of a thromboxane receptor activator or a related prostanoid.
authors.affiliation: Centro de Regulación Celular y Patología Prof. J. V. Luco, Instituto Milenio de Biología Fundamental y Aplicada, Departamento de Fisiología, Unidad de Regulación Neurohumoral, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: M Verónica
authors.initials: MV
authors.lastname: Donoso
authors.forename: Rodrigo
authors.initials: R
authors.lastname: López
authors.forename: Ramiro
authors.initials: R
authors.lastname: Miranda
authors.forename: René
authors.initials: R
authors.lastname: Briones
authors.forename: J Pablo
authors.initials: JP
authors.lastname: Huidobro-Toro
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D058917:Adenosine A2 Receptor Antagonists; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology; D016718:Arachidonic Acid / Q000378:metabolism*; D002823:Chorion / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D010920:Placenta / Q000098:blood supply; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D043704:Receptor, Adenosine A2B / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014227:Triazines / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D058917:Adenosine A2 Receptor Antagonists; D012333:RNA, Messenger; D043704:Receptor, Adenosine A2B; D014227:Triazines; D014230:Triazoles; D014665:Vasodilator Agents; D014970:Xanthines; C097270:ZM 241385; D016718:Arachidonic Acid; D019830:Adenosine-5'-(N-ethylcarboxamide); C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine