Effects of endotoxin and allergen alone and in combination on the sensitivity of the rat airways to adenosine.
1 The airways of patients with asthma are hyperresponsive to adenosine. The phenomenon can be mimicked in the actively sensitized Brown Norway rat by exposure to allergen or lipopolysaccharide (LPS). We wondered whether combined treatment with allergen and endotoxin would result in additive effects or synergism with respect to increasing the sensitivity of the airways of the Brown Norway rat to adenosine. 2 Animals actively sensitized to ovalbumin and challenged intratracheally with allergen or endotoxin manifested increased bronchoconstrictor responses to adenosine. A combination of ovalbumin and endotoxin also increased the response to adenosine but the effects were at best additive. 3 Changes in the response to adenosine were selective as responses to 5-hydroxytryptamine were unaltered following ovalbumin or LPS either alone or in combination. 4 Thus, endotoxin and allergen acting together could play a role in up-regulating the response of the human asthmatic airway to adenosine. However, our data suggest that the interaction would be additive rather than synergistic.
Karmouty Quintana
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Novartis Institutes for BioMedical Research, CH-4002 Basel, Switzerland.
Mazzoni
L
L
Fozard
J R
JR
D000241:Adenosine; D000403:Airway Resistance / Q000187:drug effects; D000485:Allergens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001980:Bronchi / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D016085:Bronchoconstrictor Agents; D004338:Drug Combinations; D004347:Drug Interactions; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D010047:Ovalbumin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011914:Rats, Inbred BN; D012701:Serotonin
D000485:Allergens; D016085:Bronchoconstrictor Agents; D004338:Drug Combinations; D004731:Endotoxins; D012701:Serotonin; D010047:Ovalbumin; D000241:Adenosine