Adenosine receptor subtypes in airways responses of sensitized guinea-pigs to inhaled ovalbumin.
Endogenous adenosine is released in asthmatic patients' lungs by inhaled allergen, however, its exact role in asthmatic responses or the receptors mediating these responses has not been determined. Our hypothesis was that adenosine released during allergen challenge contributes to the airways responses to inhaled allergen. The effects of selective antagonists of the four adenosine receptor subtypes were investigated on the airways responses of sensitized guinea-pigs to inhaled ovalbumin to ascertain the role of adenosine in these allergen responses, and compared with a corticosteroid, dexamethasone. Early (EAR) and late asthmatic responses (LAR) to inhaled ovalbumin (10 microg/ml) of sensitized, conscious guinea-pigs were recorded by whole body plethysmography following administration of selective adenosine receptor antagonists. Airway reactivity to inhaled histamine (1 mM) and inflammatory cell influx in bronchoalveolar lavage fluid were also determined 24 h after ovalbumin challenge. ZM241385 (A(2A) receptor antagonist) did not affect these responses, whereas DPCPX (A(1) receptor antagonist) exerted a small inhibition only of the LAR. MRS1706 (A(2B) receptor antagonist) inhibited the airways hyperreactivity and cellular influx and enhanced the EAR. MRS1220 (A(3) receptor antagonist) inhibited the airways hyperreactivity and cellular influx without affecting EAR and LAR. Dexamethasone inhibited the ovalbumin-induced late asthmatic responses, airways hyperreactivity and cellular influx. The blockade of airway hyperreactivity and inflammatory cell influx by A(2B) and A(3) receptor antagonists suggests that endogenous adenosine is released by inhaled allergen and these responses are mediated via A(2B) and A(3) receptors in guinea-pigs. The adenosine released by allergen inhalation does not, however, appear to be involved in the EAR, but it may contribute to the LAR via A(1) receptors.
Smith
Nicola
N
Department of Pharmacology Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cathays Park, Cardiff CF10 3NB, UK.
Broadley
Kenneth J
KJ
D000241:Adenosine / Q000276:immunology*; D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D010047:Ovalbumin / Q000276:immunology*; D010993:Plethysmography, Whole Body; D058915:Purinergic P1 Receptor Antagonists; D043704:Receptor, Adenosine A2B / Q000276:immunology*; D043684:Receptor, Adenosine A3 / Q000276:immunology*; D018047:Receptors, Purinergic P1 / Q000276:immunology; D013997:Time Factors
D058917:Adenosine A2 Receptor Antagonists; D058918:Adenosine A3 Receptor Antagonists; D005938:Glucocorticoids; D058915:Purinergic P1 Receptor Antagonists; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D003907:Dexamethasone; D010047:Ovalbumin; D000241:Adenosine