Role of endogenous adenosine in the acute and late response to allergen challenge in actively sensitized Brown Norway rats.
1. Endogenous adenosine has been suggested to amplify the response of airway mast cells to allergen in vivo. We have sought evidence for this by monitoring the acute and late-phase response to allergen in Brown Norway (BN) rats actively sensitised to ovalbumin (OA) and treated either with adenosine deaminase (ADA) linked covalently to polyethylene glycol (PEG-ADA; Adagen) to decrease adenosine availability or with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA), an inhibitor of ADA, plus S-(4-nitrobenzyl)-6-thioinosine (NBTI), an inhibitor of facilitated adenosine transport, to increase adenosine availability. 2. The cardiovascular effects of adenosine (0.01-3 mg kg(-1) i.v.) were significantly reduced in PEG-ADA-treated animals and augmented in EHNA/NBTI-treated animals. The difference in sensitivity to adenosine in the treated groups was 33- and 15-fold, at the level of 30% reduction in blood pressure and heart rate, respectively. 3. The acute response to allergen, given either intravenously or intratracheally, was quantified as bronchoconstriction. The late phase to allergen was measured as the influx and activation of immunoinflammatory cells into the bronchoalveolar lavage fluid 24 h after challenge. 4. Despite evidence of a substantial difference in adenosine availability following pretreatment with PEG-ADA or EHNA/NBTI, there were no differences in either the acute or late response to allergen in the actively sensitised BN rat. 5. Our data suggest no role for endogenous adenosine in determining the response to allergen under our experimental conditions.
Ellis
K M
KM
Research Department, Novartis Pharma AG, WSJ 386.510, CH-4002 Basel, Switzerland.
Mazzoni
L
L
Fozard
J R
JR
D000241:Adenosine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000008:administration & dosage; D000485:Allergens / Q000008:administration & dosage*; D000818:Animals; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects* / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007275:Injections, Intravenous; D007442:Intubation, Intratracheal; D008297:Male; D010047:Ovalbumin / Q000008:administration & dosage; D051381:Rats; D011914:Rats, Inbred BN; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000503:physiopathology
D000485:Allergens; D010047:Ovalbumin; D000243:Adenosine Deaminase; C051409:pegademase bovine; D000241:Adenosine