Substance P- and antigen-induced release of leukotriene B-4, prostaglandinD-2 and histamine from guinea pig skin by different mechanisms in vitro

Substance P (SP) induces increased vascular permeability, vasodilatation an d granulocyte infiltration upon intradermal injection. Studies with antagon ists and mast cell-deficient mice have suggested that granulocyte infiltrat ion in response SP is mediated by leukotriene (LT) B-4 derived from mast ce lls, However, the release of LTB4 has not been detected using mast cells is olated from human skin. Here we report the release of LTB4, prostaglandin ( PG) D-2 and histamine from guinea pig skin tissue in response to SP, The re lease of these agents occurred in a dose-dependent manner over a concentrat ion range of SP from 1 x 10(-6) to 3 x 10(-4) M, No detectable PGE, was rel eased 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 anti gen. By comparison, SP-induced and antigen-induced release of LTB4 and PGD, were similar, but slower than the histamine release, In the absence of ext racellular Ca2+, release of histamine and PGD, in response to SP was partia lly impaired, but to a lesser extent than that induced by antigen, On the o ther hand, LTB4 release in response to both SP and antigen was abolished un der the same conditions. These results indicate that SP induces the release of LTB4, as well as histamine and PGD(2), in the skin most likely from mas t cells by a mechanism which may be different from that of mediator release in response to antigen.