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

2 Citations (Scopus)

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

Fingerprint

Adenosine A3 Receptor Agonists
Adenosine A1 Receptor Agonists
Trachea
Guinea Pigs
Adenosine
Nitric Oxide Synthase Type I
Adenosine A3 Receptors
Quinazolines
Adenosine A1 Receptors
Neurons
Membranes
Ion Exchange
Indirect Fluorescent Antibody Technique
Neurotransmitter Agents
Immunohistochemistry
1,3-dipropyl-8-cyclopentylxanthine
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea. / Dellabianca, Antonio; Faniglione, Marisa; De Angelis, Stefano; Tonini, Stefano; Balestra, Barbara; Colucci, Mario; Cervio, Marila; Clavenzani, Paolo; Chiocchetti, Roberto; De Giorgio, Roberto; Candura, Stefano M.

In: Respiration, Vol. 78, No. 1, 07.2009, p. 75-83.

Research output: Contribution to journalArticle

Dellabianca, A, Faniglione, M, De Angelis, S, Tonini, S, Balestra, B, Colucci, M, Cervio, M, Clavenzani, P, Chiocchetti, R, De Giorgio, R & Candura, SM 2009, 'Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea', Respiration, vol. 78, no. 1, pp. 75-83. https://doi.org/10.1159/000183755
Dellabianca, Antonio ; Faniglione, Marisa ; De Angelis, Stefano ; Tonini, Stefano ; Balestra, Barbara ; Colucci, Mario ; Cervio, Marila ; Clavenzani, Paolo ; Chiocchetti, Roberto ; De Giorgio, Roberto ; Candura, Stefano M. / Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea. In: Respiration. 2009 ; Vol. 78, No. 1. pp. 75-83.
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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.",
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T1 - Adenosine A1 and A3 receptor agonists inhibit nonadrenergic, noncholinergic relaxations in the guinea pig isolated trachea

AU - Dellabianca, Antonio

AU - Faniglione, Marisa

AU - De Angelis, Stefano

AU - Tonini, Stefano

AU - Balestra, Barbara

AU - Colucci, Mario

AU - Cervio, Marila

AU - Clavenzani, Paolo

AU - Chiocchetti, Roberto

AU - De Giorgio, Roberto

AU - Candura, Stefano M.

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

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KW - Inhibitory nonadrenergic, noncholinergic innervation

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