Effects of selective and non-selective COX inhibitors on antigen-induced release of prostanoid mediators and bronchoconstriction in the isolated perfused and ventilated guinea pig lung.

The contribution of cycloxygenase (COX)-1 and COX-2 in antigen-induced release of mediators and ensuing bronchoconstriction was investigated in the isolated perfused guinea pig lung (IPL). Antigen challenge with ovalbumin (OVA) of lungs from actively sensitised animals induced release of thromboxane (TX)A2, prostaglandin (PG)D2, PGF2α, PGI2 and PGE2, measured in the lung effluent as immunoreactive TXB2, PGD2-MOX, PGF2α, 6-keto PGF1α and PGE2, respectively. This release was abolished by the non-selective COX inhibitor flurbiprofen (10μM). In contrast, neither the selective COX-1 inhibitor FR122047 nor the selective COX-2 inhibitor celecoxib (10μM each) significantly inhibited the OVA-induced bronchoconstriction or release of COX products, except for PGD2. Another non-selecive COX inhibitor, diclofenac (10μM) also significantly inhibited antigen-induced bronchoconstriction. The data suggest that both COX isoenzymes, COX-1 and COX-2 contribute to the immediate antigen-induced generation of prostanoids in IPL and that the COX-1 and COX-2 activities are not associated with different profiles of prostanoid end products.