Effects of selected antagonists on ovalbumin-induced contraction of tracheal strips isolated from the actively sensitized guinea-pig

Antigen‐induced contraction of guinea‐pig isolated trachea: studies with novel inhibitors and antagonists of arachidonic acid metabolites

“…Most studies concur that contractile responses are the result of the collective actions and interactions of released histamine and arachidonic acid metabolites generated via the 5-lipoxygenase (leukotrienes C4, D4 and E4) and cyclo-oxygenase (prostaglandins, endoperoxide and thromboxane) enzyme systems (Adams & Lichtenstein, 1979;Hand & Buckner, 1979;Burka & Paterson, 1980;Burka & Paterson, 1981b;Hand et al, 1986). A major role for 5-lipoxygenase products in the mediation of the response has been postulated based on pharmacological studies with FPL-55712 and some relatively weak 5-lipoxygenase inhibitors (Adams & Lichtenstein, 1979;Hand & Buckner, 1979;Burka & Paterson, 1980;Hand et al, 1986).…”

“…The nature of the mediators and mechanisms involved in ' Author for correspondence. this response have been the subject of extensive biochemical and pharmacological investigation over the years (Chand & Eyre, 1978;Adams & Lichtenstein, 1979;Hand & Buckner, 1979;Burka & Paterson, 1980;1981ab;Saad et al, 1983;De Nucci et al, 1986). Conclusions about the precise contribution of various mediators to the contractile response vary depending on the species studied (Dunlop & Smith, 1975;Dunlop et al, 1977;Dahlen et al, 1983;Jones et al, 1987), the type of antibody mediating the response (Andersson, 1980;Regal, 1984;Undem et al, 1985) the nature of the experiment (biochemical or functional response) and the experimental conditions such as the presence or absence of additional blocking drugs (Hand et al, 1986).…”

“…Antigen-induced contraction of isolated trachealis from actively or passively sensitized guinea-pigs has been used by many investigators as a model of immediate hypersensitivity (Chand & Eyre, 1978;Adams & Lichtenstein, 1979;Hand & Buckner, 1979;Burka & Paterson, 1980;1981ab). Similarly, contraction to antigen can be elicited in passively (Dunlop & Smith, 1975;Dunlop et al, 1977;Adams & Lichtenstein, 1979;Davis et al, 1982) and intrinsically sensitized human tracheobronchial smooth muscle (Davis et al, 1982;Dahlen et al, 1983).…”

Modulation of in vitro anaphylaxis of guinea‐pig isolated tracheal segments by azelastine, inhibitors of arachidonic acid metabolism and selected antiallergic drugs

“…At this concentration azelastine also inhibited (P < 0.05) the indomethacin-augmented component of initial and secondary phases ofanaphylactic responses ofguineapig isolated tracheal segments. BW 755c (1O gM) only prolonged (P <0.05) the duration of onset of the allergic response with little or no effect on the duration of peak effect and the magnitude of anaphylactic ;Chand, 1979, a,b;Hand & Buckner, 1979;Burka & Paterson, 1980;Chand & Altura, 1981;Samuelsson, 1983;Adams & Lichtenstein, 1985). The blockade of the indomethacin-augmented airway responses (the time course of the development of anaphylactic responses) by BW 755c and azelastine (50-100 JLM) also suggests the involvement of the products of leukotriene synthetase pathway of arachidonic acid metabolism in the mediation of allergic tracheal responses.…”

“…Indomethacin, a potent cyclo-oxygenase inhibitor, has been reported to augment allergic responses in guinea-pig isolated trachea (Hand & Buckner, 1979;Burka & Paterson, 1980) and human bronchus (Adam & Lichtenstein, 1985). In this study the effects of azelastine on the indomethacin-augmented component of allergic responses in guinea-pig isolated tracheal segments were investigated and compared with selected antiallergic drugs and agents that are known to interfere with arachidonic acid metabolism.…”