SKIN-RESPONSES TO BRADYKININ, KALLIDIN, AND [DESARG(9)]-BRADYKININ INNONATOPIC AND ATOPIC VOLUNTEERS

Background: Kinins are potent vasoactive oligopeptides that may act as mediators in a variety of inflammatory diseases of the skin by intera cting with specific receptors designated B1 and B2 In this study we ha ve investigated the structure-activity relationship of intradermally i njected bradykinin, kallidin (lysine-bradykinin), and [desArg9]-bradyk inin in atopic (n = 8) and nonatopic (n = 8) subjects. Methods: On two separate occasions, each separated by a week, subjects randomly under went intradermal challenge with incremental doses (0.5, 5, and 50 nmol ) of either the B1-agonist [desArg9]-bradykinin, the B2-agonists brady kinin or kallidin, or vehicle placebo. In a separate randomized double -blind study we have also examined the effect of an orally administere d antihistamine, terfenadine, on kinin-induced wheal and flare respons es and their repeatability in a group of nine volunteers. The skin res ponses were monitored objectively by measurement of wheal and flare ar eas. Results: Both bradykinin and kallidin induced a dose-dependent in crease in wheal and flare areas in all subjects studied. Although the effects of the two lowest doses (0.5 and 5 nmol) of [desArg9]-bradykin in on skin responses were indistinguishable from those of placebo, thi s kinin at the highest dose administered (50 nmol) caused a significan t increase in wheal and flare areas in all subjects studied. No differ ence could be identified in the skin responses to kinins between atopi c and nonatopic subjects. In addition kinin-induced cutaneous response s were not altered by pretreatment with terfenadine. Conclusions: Thes e in vivo structure activity studies suggest that in human beings the skin responses to kinins may be compatible with the stimulation of B2 receptors, which is unrelated to histamine release from cutaneous mast cells.