RESUMO
The effect of toxic oxygen metabolite scavengers was examined in a guinea pig trachealis model of leukotriene (LTD4)-induced synergism upon histamine contractures. Under both physiologic (2.5 mM) and low (OmM) extracellular calcium conditions, LTD4 (10(-7) to 10(-9) M) potentiated histamine isometric tension responses. This LTD4-induced histamine hyperresponse was inhibited by pretreatment with superoxide dismutase. Inhibition of LTD4 receptor binding by FPL 55712 (10(-5) M) also aborted this interaction. Actual trachealis superoxide anion (O2-) generation by LTD4 was observed with a maximal release of 15 nM O2-/CPK unit X 10(-2) over 60 min. Phorbol myristate acetate (PMA) also generated O2- in this preparation. Trachealis muscle hyperreactivity to histamine induced by 10(-8) M LTD4 assayed in OmM (Ca++)E was not induced by PMA. It is concluded that exogenous LTD4 activates toxic oxygen metabolites which interact to induce an acquired hyperreactivity to agonist histamine in trachealis smooth muscle.
Assuntos
Consumo de Oxigênio , Oxigênio/toxicidade , Hipersensibilidade Respiratória/etiologia , SRS-A/farmacologia , Animais , Cromonas/farmacologia , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Cobaias , Histamina/farmacologia , Técnicas In Vitro , Contração Isométrica/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Receptores de Leucotrienos , Receptores de Prostaglandina/efeitos dos fármacos , Receptores de Prostaglandina/metabolismo , Hipersensibilidade Respiratória/fisiopatologia , SRS-A/antagonistas & inibidores , SRS-A/metabolismo , Superóxido Dismutase/toxicidade , Superóxidos/toxicidade , Acetato de Tetradecanoilforbol/farmacologiaRESUMO
Extracellular release of superoxide anion (O-2) during in vitro anaphylaxis in guinea pig trachealis was found to exhibit both a time- and a concentration-dependent generation of O-2. Trachealis O-2 release was unaffected by treatment with diphenhydramine HCl (10(-5) M, 10(-6) M). While indomethacin (10(-5) M) augmented anaphylaxis tension it did not enhance O-2 release. However, the semiselective SRS-A antagonist FPL 55712 (10(-5) M) resulted in essentially complete inhibition of O-2 generation. These data indicate that O-2 generation occurring during acute airway anaphylaxis is associated with the activation of SRS-A products.