Substance P- and antigen-induced release of leukotriene B₄, prostaglandin D₂ and histamine from guinea pig skin by different mechanisms in vitro

Abstract Substance P (SP) induces increased vascular permeability, vasodilatation and granulocyte infiltration upon intradermal injection. Studies with antagonists and mast cell-deficient mice have suggested that granulocyte infiltration in response SP is mediated by leukotriene (LT) B₄ derived from mast cells. However, the release of LTB₄ has not been detected using mast cells isolated from human skin. Here we report the release of LTB₄, prostaglandin (PG) D₂ and histamine from guinea pig skin tissue in response to SP. The release of these agents occurred in a dose-dependent manner over a concentration range of SP from 1 × 10^–6 to 3 × 10^–4 M. No detectable PGE₂ was released at any concentration up to 3 × 10^–4 M SP. The kinetics of histamine release induced in response to SP was more rapid than that induced by antigen. By comparison, SP-induced and antigen-induced release of LTB₄ and PGD₂ were similar, but slower than the histamine release. In the absence of extracellular Ca²⁺, release of histamine and PGD₂ in response to SP was partially impaired, but to a lesser extent than that induced by antigen. On the other hand, LTB₄ release in response to both SP and antigen was abolished under the same conditions. These results indicate that SP induces the release of LTB₄, as well as histamine and PGD₂, in the skin most likely from mast cells by a mechanism which may be different from that of mediator release in response to antigen.