Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea

Antonio Dellabianca, Marisa Faniglione, Stefano De Angelis, Stefano Tonini, Barbara Balestra, Mario Colucci, Marila Cervio, Paolo Clavenzani, Roberto Chiocchetti, Roberto De Giorgio, Stefano M. Candura

Research output: Contribution to journalArticle

Abstract

Background: Adenosine affects the tone and reactivity of airways by activating specific membrane receptors, named A1, A2a, A2b and A3. It affects cellular activities either directly by regulating membrane ion exchanges and polarization, or indirectly by modifying neurotransmitter release. Objectives: We assessed the effect of A 1 and A3 receptor activation on electrically induced nonadrenergic, noncholinergic (NANC) relaxations in the guinea pig isolated trachea and the localization of A1 and A3 receptors in tracheal inhibitory neurons. Methods: NANC responses at 3 Hz were evaluat- ed in the presence of 2-chloro-N6-cyclopentyladenosine (CCPA), a selective A1 agonist, and 2-chloro-N6-(3-iodobenzyl)-adenosine- 5′-N-methyluronamide (Cl-IB-MECA), a selective A3 agonist, before and after the administration of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A1ntagonist, or 9-chloro-2-(2-furanyl)-5- ((phenylacetyl)amino[1,2,4]triazolo[1,5-c])quinazoline (MRS 1220), a selective A3 antagonist, respectively. For immunohistochemistry, tissues were exposed to antibodies to HuC/D, a general neuronal marker, neuronal nitric oxide synthase (nNOS), and A1 or A3 adenosine receptors and processed by indirect immunofluorescence. Results: CCPA (10 nM-3 μM) inhibited NANC relaxations. DPCPX (10 nM) failed to antagonize the effect of CCPA, but inhibited per se NANC relaxations (range 0.1-100 nM). CCPA (10 nM-10 μM) contracted unstimulated tracheal preparations, an effect antagonized by 10 nM DPCPX, with a pKB value of 8.43. Cl-IB-MECA (10 nM-3 μM) inhibited NANC relaxations through a mechanism antagonized by MRS 1220 (100 nM). A1- and A3-positive neurons containing nNOS were detected in tracheal sections. Conclusions: Enogenous adenosine may induce airway hyperresponsiveness by inhibiting NANC relaxations via A1 and A3 receptors.

Original languageEnglish
Pages (from-to)75-83
Number of pages9
JournalRespiration
Volume78
Issue number1
DOIs
Publication statusPublished - Jul 2009

Keywords

  • Adenosine
  • Airways
  • Guinea pig
  • Inhibitory nonadrenergic, noncholinergic innervation
  • Trachea

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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    Dellabianca, A., Faniglione, M., De Angelis, S., Tonini, S., Balestra, B., Colucci, M., Cervio, M., Clavenzani, P., Chiocchetti, R., De Giorgio, R., & Candura, S. M. (2009). Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea. Respiration, 78(1), 75-83. https://doi.org/10.1159/000183755