Substance P and Arg-Pro-Lys-Pro-NH-C12-H25-induced mediator release from different mast cell subtypes of rat and guinea-pig.

Histamine was released from mast cells in isolated perfused heart and kidney of the rat, but not from mast cells in guinea-pig tissues, by a substance P (SP) analogue (SP(1-4)-NH-C12H25), SP(1-4)-C12 for abbreviation. This peptide also released histamine from peritoneal mast cells and basophil leucocytes of the rat. Substance P itself was compared with SP(1-4)-C12 and some structurally related peptides and showed weaker activity. SP(1-4)-C12 also released leukotrienes C4, D4, E4 and thromboxane B2 from rat heart. However, there was little effect on heart rate and force of contraction and no effect on perfusion pressure (vascular resistance) of either rat heart or kidney. The findings demonstrate the structural requirements for histamine release by SP (a possible mediator of 'neurogenic' inflammation), the metabolic energy-dependence of the release process and the functional heterogeneity and interspecies differences in mast cell populations.