In:
Respiration, S. Karger AG, Vol. 78, No. 1 ( 2009), p. 75-83
Abstract:
〈 i 〉 Background: 〈 /i 〉 Adenosine affects the tone and reactivity of airways by activating specific membrane receptors, named A 〈 sub 〉 1 〈 /sub 〉 , A 〈 sub 〉 2a 〈 /sub 〉 , A 〈 sub 〉 2b 〈 /sub 〉 and A 〈 sub 〉 3 〈 /sub 〉 . It affects cellular activities either directly by regulating membrane ion exchanges and polarization, or indirectly by modifying neurotransmitter release. 〈 i 〉 Objectives: 〈 /i 〉 We assessed the effect of A 〈 sub 〉 1 〈 /sub 〉 and A 〈 sub 〉 3 〈 /sub 〉 receptor activation on electrically induced nonadrenergic, noncholinergic (NANC) relaxations in the guinea pig isolated trachea and the localization of A 〈 sub 〉 1 〈 /sub 〉 and A 〈 sub 〉 3 〈 /sub 〉 receptors in tracheal inhibitory neurons. 〈 i 〉 Methods: 〈 /i 〉 NANC responses at 3 Hz were evaluat- ed in the presence of 2-chloro-N 〈 sup 〉 6 〈 /sup 〉 -cyclopentyladenosine (CCPA), a selective A 〈 sub 〉 1 〈 /sub 〉 agonist, and 2-chloro-N 〈 sup 〉 6 〈 /sup 〉 -(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA), a selective A 〈 sub 〉 3 〈 /sub 〉 agonist, before and after the administration of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A 〈 sub 〉 1 〈 /sub 〉 antagonist, or 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino[1,2,4]triazolo[1,5-c] )quinazoline (MRS 1220), a selective A 〈 sub 〉 3 〈 /sub 〉 antagonist, respectively. For immunohistochemistry, tissues were exposed to antibodies to HuC/D, a general neuronal marker, neuronal nitric oxide synthase (nNOS), and A 〈 sub 〉 1 〈 /sub 〉 or A 〈 sub 〉 3 〈 /sub 〉 adenosine receptors and processed by indirect immunofluorescence. 〈 i 〉 Results: 〈 /i 〉 CCPA (10 n 〈 i 〉 M 〈 /i 〉 –3 μ 〈 i 〉 M 〈 /i 〉 ) inhibited NANC relaxations. DPCPX (10 n 〈 i 〉 M 〈 /i 〉 ) failed to antagonize the effect of CCPA, but inhibited per se NANC relaxations (range 0.1–100 n 〈 i 〉 M 〈 /i 〉 ). CCPA (10 n 〈 i 〉 M 〈 /i 〉 –10 μ 〈 i 〉 M 〈 /i 〉 ) contracted unstimulated tracheal preparations, an effect antagonized by 10 n 〈 i 〉 M 〈 /i 〉 DPCPX, with a pK 〈 sub 〉 B 〈 /sub 〉 value of 8.43. Cl-IB-MECA (10 n 〈 i 〉 M 〈 /i 〉 –3 μ 〈 i 〉 M 〈 /i 〉 ) inhibited NANC relaxations through a mechanism antagonized by MRS 1220 (100 n 〈 i 〉 M 〈 /i 〉 ). A 〈 sub 〉 1 〈 /sub 〉 - and A 〈 sub 〉 3 〈 /sub 〉 -positive neurons containing nNOS were detected in tracheal sections. 〈 i 〉 Conclusions: 〈 /i 〉 Enogenous adenosine may induce airway hyperresponsiveness by inhibiting NANC relaxations via A 〈 sub 〉 1 〈 /sub 〉 and A 〈 sub 〉 3 〈 /sub 〉 receptors.
Type of Medium:
Online Resource
ISSN:
0025-7931
,
1423-0356
Language:
English
Publisher:
S. Karger AG
Publication Date:
2009
detail.hit.zdb_id:
1464419-8
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