We have explored the effects of bacterial
endotoxin (
lipopolysaccharide; LPS) on the response of the airways of Brown Norway (BN) rats to
adenosine. Comparisons have been drawn with the effects on responses to
methacholine and
5-hydroxytryptamine. In vehicle-challenged animals,
adenosine, given i.v. was only a weak bronchoconstrictor. In contrast, 1 h following intratracheal administration of LPS, 0.3 mg kg-1, bronchoconstrictor responses to
adenosine were markedly and selectively enhanced. At this time point, there were no significant changes in leukocyte numbers,
eosinophil peroxidase and
myeloperoxidase activities or
protein concentrations in bronchoalveolar lavage (BAL) fluid. Twenty-four hours after challenge, the sensitivity of the airways to both
adenosine and
methacholine was reduced relative to the earlier time point and there were substantial increases in each marker of
inflammation in BAL fluid. The bronchoconstrictor response to
adenosine was blocked selectively by
methysergide,
disodium cromoglycate and the broad-spectrum
adenosine receptor antagonist, 8-SPT, but not by
DPCPX or ZM 243185, selective antagonists for the A1 and A2A receptors, respectively. Thus, the response to
adenosine augmented following LPS is mast cell mediated and involves a receptor which can be blocked by 8-SPT but not by selective A1 or A2A receptor antagonists. It thus bears similarity to the augmented response to
adenosine induced by
allergen challenge in actively sensitized BN rats. Exposure to LPS could be
a factor along with
allergen in determining the increased sensitivity of the airways of asthmatics to
adenosine.