title: Pharmacological characterization of adenosine receptors on isolated human bronchi.
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 A(1) 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 A(1) > A(2B) >> A2(A) = A3. The maximum contractile response to N(6)-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 A(1) 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 A(1) receptors in eliciting human airway smooth muscle constriction, which, in part, is mediated by the action of capsaicin sensitive sensory nerves.
authors.affiliation: Department of Internal Medicine, University of Rome "Tor Vergata," Italy.
authors.forename: Luigino
authors.initials: L
authors.lastname: Calzetta
authors.forename: Domenico
authors.initials: D
authors.lastname: Spina
authors.forename: Mario
authors.initials: M
authors.lastname: Cazzola
authors.forename: Clive P
authors.initials: CP
authors.lastname: Page
authors.forename: Francesco
authors.initials: F
authors.lastname: Facciolo
authors.forename: Erino A
authors.initials: EA
authors.lastname: Rendina
authors.forename: Maria G
authors.initials: MG
authors.lastname: Matera
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D058907:Adenosine A1 Receptor Agonists / Q000494:pharmacology*; D019830:Adenosine-5'-(N-ethylcarboxamide) / Q000494:pharmacology*; D001249:Asthma / Q000378:metabolism / Q000503:physiopathology*; D001980:Bronchi / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009924:Organ Culture Techniques; D043682:Receptor, Adenosine A1; D018689:Sensory System Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D058907:Adenosine A1 Receptor Agonists; D043682:Receptor, Adenosine A1; D018689:Sensory System Agents; D014665:Vasodilator Agents; D019830:Adenosine-5'-(N-ethylcarboxamide); C048599:N(6)-cyclopentyladenosine; D000241:Adenosine; D002211:Capsaicin