Studies on the relationship between contraction and mediator release produced by ovalbumin in superfused trachea isolated from the actively sensitized guinea pig

Abstract

The temporal relationship between release of the mediators histamine and slow reacting substance of anaphylaxis (SRS-A) and smooth muscle contraction in response to antigen was examined using superfused tracheae from actively sensitized (ovalbumin) and reserpine-pretreated guinea pigs. Maximum contraction occurred simultaneously with the maximum amount of histamine appearing in the superfusate, but the dose-response curves of ovalbumin were different for the two responses. The peak appearance of SRS-A in the superfusate was more delayed than that of peak histamine or contraction. After antigen-induced desensitization, histamine and SRS-A release evoked by rechallenge with antigen were reduced to a greater extent than was contraction. Indomethacin, 5 X 10(-6) M, did not alter mediator release but enhanced the height of contraction produced by a submaximum concentration of ovalbumin and impeded return to basal tension, 5,8,11,14-Eicosatetraynoic acid, 10(-5) M, in combination with indomethacin reduced the magnitude of this contraction and reduced by 50% the total SRS-A released without altering histamine release. 5,8,11,14-Eicosatetraynoic acid increased the magnitude of contraction observed after desensitization without altering mediator release. Addition of mepyramine, 10(-6) M, and FPL55712, 10(-5) M, to the superfusion solution reduced the magnitude of the contractions produced by ovalbumin in the absence of prior desensitization but had no effect on the contractions produced after desensitization. Histamine release was unaltered by these treatments. Although histamine and SRS-A appear to play a role in airway smooth muscle contraction, other unidentified mediator(s) may also be involved in the contractile response to antigen, especially after desensitization.