Adenosine receptor subtypes in the airways responses to 5 '-adenosine monophosphate inhalation of sensitized guinea-pigs

Smith, N. and Broadley, Kenneth John ORCID: https://orcid.org/0000-0002-3339-2050 2008. Adenosine receptor subtypes in the airways responses to 5 '-adenosine monophosphate inhalation of sensitized guinea-pigs. Clinical and Experimental Allergy 38 (9) , pp. 1536-1547. 10.1111/j.1365-2222.2008.03034.x

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Abstract

Background Endogenous adenosine levels are raised in the lungs during asthma attacks. 5′-adenosine monophosphate (5′-AMP) inhalation in asthmatics causes bronchoconstriction and in sensitized guinea-pigs induces early (EAR) and late asthmatic responses (LAR), airway hyper-reactivity (AHR) and inflammatory cell recruitment to the lungs. Objective The aim of this study was to investigate the roles of A1, A2A, A2B and A3 adenosine receptors in these responses to inhaled 5′-AMP in sensitized guinea-pigs. Comparisons were made with the effect of dexamethasone treatment on 5′-AMP-induced responses. Methods Functional airways responses to inhaled 5′-AMP (3 and 300 mm) of actively sensitized, conscious guinea-pigs were determined by whole-body plethysmography following administration of selective adenosine receptor antagonists or their vehicles. AHR to inhaled histamine (1 mm) and inflammatory cell influx in bronchoalveolar lavage fluid were determined. Results 5′-AMP at 3 mm caused an immediate bronchoconstriction (EAR), whereas 300 mm caused bronchodilatation. Both responses were followed at 6 h by a LAR, together with inflammatory cell influx and AHR to histamine. The A2A receptor antagonist, ZM241385, further enhanced cell influx after 5′-AMP inhalation (3 and 300 mm), and blocked the immediate bronchodilator response to 300 mm 5′-AMP, exposing an EAR. The A2B receptor antagonist, MRS1706 (in the presence of ZM241385), inhibited the LAR, AHR and cell influx, following inhalation of 5′-AMP (300 mm). The A3 receptor antagonist, MRS1220, inhibited 5′-AMP-induced inflammatory cell influx. The A1 receptor antagonist, DPCPX (in the presence of ZM241385), inhibited the EAR following 5′-AMP inhalation (300 mm). Dexamethasone inhibited the LAR, AHR and cell influx following inhalation of 5′-AMP (300 mm). Conclusion All four adenosine receptor subtypes play various roles in the airways responses to inhaled 5′-AMP in sensitized guinea-pigs.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Pharmacy
Subjects:	R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	adenosine receptor subtypes ; 5′-AMP ; AHR ; EAR ; inflammatory cell influx ; LAR ; sensitized guinea-pigs
Publisher:	Blackwell Scientific
ISSN:	0954-7894
Last Modified:	17 Oct 2022 10:04
URI:	https://orca.cardiff.ac.uk/id/eprint/6732

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