The simultaneous evaluation of platelet behaviour in vivo and of the accompanying bronchoconstriction in the guinea pig is described.
Arachidonic acid induces bronchoconstriction, accompanied by, but independent from,
thrombocytopenia, whereas
collagen induces bronchoconstriction also accompanied by, but dependent from,
thrombocytopenia. In both cases bronchoconstriction is due to
cyclo-oxygenase metabolites of
arachidonic acid. Use of potential inhibitors of
thromboxane synthetase failed to reveal which of
prostaglandin endoperoxides or
thromboxane A2 is responsible for
aspirin-inhibitive bronchoconstriction and
thrombocytopenia. In contrast to
PGE1 prostacyclin failed to interfere with bronchoconstriction by
serotonin or by
arachidonic acid, even though
thrombocytopenia by the latter was suppressed. Bronchoconstriction by
collagen, in contrast, was inhibited by nanogram doses of
prostacyclin, confirming platelet-dependency. The combined bronchoconstriction/
thrombocytopenia test in guinea pigs can discriminate sites of action of anti-inflammatory drugs, of agents which block specific platelet and/or bronchial receptors, which stimulate the
cyclic AMP system, or generically which interfere with the mechanisms of bronchoconstriction and of
thrombocytopenia.