The contractile activity and mobilisation of
arachidonic acid metabolites in response to the
antigen challenge were studied in isolated lung parenchymal tissue from the actively sensitised guinea pig. The sustained constriction of the lung tissue was evoked by the
antigen, associated with significant liberation of TXB2,
histamine and p-LTs. Other
prostanoids (
PGF2 alpha,
PGD2,
PGE2 and
6-keto-PGF1 alpha) were also released by the
antigen challenge.
DP-1904, an inhibitor of TX
synthetase, significantly suppressed the late phase of the
antigen-induced constriction.
DP-1904 was potent to inhibit the production of TXB2, while
DP-1904 accelerated the formation of
PGF2 alpha,
PGE2 and
6-keto-PGF1 alpha, presumably indicating the alternative changes of dilatory metabolites to the spasmogenic component.
Mepyramine and FPL-77512 augmented the effect of
DP-1904.
AA-861 inhibited the
antigen-induced constriction of the lung parenchymal tissue by inhibiting the release of p-LTs and TXB2. Pretreatment of the lung parenchymes with anti-guinea pig platelet serum, in order to deplete the platelets, did not affect the generation of TXB2 both in resting and also in the
antigen-stimulated status, indicating that TXA2 is produced in the topical pulmonary tissue. It is concluded that
DP-1904 inhibits the parenchymal contraction through potent inhibition of TXA2 generation, associated with significant elevation in
PGE2 and PGI2.