Pharmacological characterization of adenosine receptors on isolated human bronchi

Luigino Calzetta, Domenico Spina, Mario Cazzola, Clive P. Page, Francesco Facciolo, Erino A. Rendina, Maria G. Matera

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Abstract

Adenosine induces airways obstruction in subjects with asthma, but the receptor subtype responsible remains unknown. The objectives of this study were to determine the pharmacological profile of adenosine receptor subtypes mediating contraction and to investigate the mechanism in normal and passively sensitized human airway tissues. Contraction of bronchial rings isolated from resected lung tissue of patients with lung carcinoma was measured in response to nonselective adenosine receptor agonists, 5-AMP and 5′-(N- Ethylcarboxamido)adenosine, and A1 receptor agonist, N 6-cyclopentyladenosine, in the absence and presence of selective adenosine receptor antagonists. Pharmacological antagonists, chemical ablation of airway sensory nerves using capsaicin, and passive sensitization of tissue with serum from subjects with atopy and asthma was used to investigate the mechanism of contraction. Human bronchial tissue contracted in a concentration-dependent manner to adenosine agonists that showed a rank order of activity of A1 > A2B ≫ A2A = A3. The maximum contractile response to N6-cyclopentyladenosine (231.0 ± 23.8 mg) was significantly reduced in tissues chemically treated with capsaicin to desensitize sensory nerves (desensitized: 101.6 ± 15.2 mg; P <0.05). Passive sensitization significantly augmented the contraction induced by adenosine A1 receptor activation (sensitized: 389.7 ± 52.8 mg versus nonsensitized; P <0.05), which was linked to the release of leukotrienes, and not histamine (MK571: 25.5 ± 1.7 mg; epinastine 260.0 ± 22.2 mg versus control; P <0.05). This study provides evidence for a role for adenosine A1 receptors in eliciting human airway smooth muscle constriction, which, in part, is mediated by the action of capsaicin sensitive sensory nerves.

Original languageEnglish
Pages (from-to)1222-1231
Number of pages10
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume45
Issue number6
Publication statusPublished - Dec 1 2011

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Keywords

  • Adenosine
  • Airway smooth muscle contraction
  • Human bronchi
  • N-cyclopentyladenosine

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

Cite this

Calzetta, L., Spina, D., Cazzola, M., Page, C. P., Facciolo, F., Rendina, E. A., & Matera, M. G. (2011). Pharmacological characterization of adenosine receptors on isolated human bronchi. American Journal of Respiratory Cell and Molecular Biology, 45(6), 1222-1231.