Effects of forskolin and prostaglandin E1 on leukotriene C- and D-induced plasma exudation in the rat skin.

Leukotriene C and D markedly enhanced plasma exudation in rat skin, using [131I]-labeled human serum albumin ([131I]-HSA) to measure vascular permeability. The adenylate cyclase activator forskolin only slightly increased plasma exudation, while markedly potentiating the leukotriene response. Prostaglandin E1 increases plasma exudation in rat skin, but appears to act by a different mechanism than leukotrienes, since the responses to combinations of prostaglandin and leukotrienes are synergistic and the responses to prostaglandins are inhibited by forskolin. The phosphodiesterase inhibitor, isobutylmethylxanthine also potentiated the leukotriene C-induced response. The effects of the various agents on leukotriene responses are similar to effects of these agents on bradykinin and histamine-induced plasma exudation. These results suggest that an increase in the cyclic AMP in the rat skin, elicited by forskolin or prostaglandin potentiates the leukotriene C and D-induced plasma exudation and that leukotriene C and D increase the vascular permeability through the same type of mechanism that pertains for histamine and bradykinin.