Peptide and non-
peptide kinin receptor antagonists were evaluated in cutaneous
inflammation models in mice. Topical and i.p. application of
kinin B(1) and
B(2) receptor antagonists caused a significant inhibition of the
capsaicin-induced cutaneous neurogenic inflammatory response. The calculated mean ID(50) for
Hoe140 and
SSR240612 were 23.83 (9.14-62.14) nmol/kg and 0.23 (0.15-0.36) mg/ear, respectively. The I(max) observed for
Hoe140,
SSR240612,
R-715,
FR173657, and FR plus SSR were 61+/-5%, 56+/-3%, 65+/-10%, 48+/-8%, and 52+/-4%, respectively. Supporting these results, double B(1) and
B(2)
kinin receptors knockout mice showed a significant inhibition of
capsaicin-induced ear oedema (42+/-7%). However, mice with a single deletion of either B(1) or
B(2) receptors exhibited no change in their
capsaicin responses. In contrast, all of the examined
kinin receptor antagonists were unable to inhibit the oedema induced by TPA and the results from knockout mice confirmed the lack of
kinin receptor signaling in this model. These findings show that
kinin receptors are present in the skin and that both
kinin receptors seem to be important in the neurogenic inflammatory response. Moreover, non-
peptide antagonists were very effective in reducing skin
inflammation when topically applied, thereby suggesting that they could be useful tools in the treatment of some skin inflammatory diseases.