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 x 10(-6) to 3 x 10(-4) M. No detectable PGE2 was released at any concentration up to 3 x 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.