Substance P causes adhesion of neutrophils to endothelial cells via protein kinase C

The sensory neuropeptide substance P is known to be involved in neurogenic inflammation, We examined the effect of substance P on neutrophil adhesion to human umbilical vein endothelial cells (HUVEC). Stimulation of HUVEC wit h substance P increased their adhesion to neutrophils in a time- and concen tration (10(-10)-10(-7) M)-dependent manner, The adhesion was inhibited by the tachykinin NK1 receptor antagonist (+)-(2S,3S)-3-(2-Methoxybenzylamino) -2-phenylpiperidine (CP-99,994) and also by the protein kinase C inhibitors 1-(5-Iso-quinolinesulfonyl)-2-methyl piperazine (H-7) and bisindolylmaleim ide (BIM), but not by the protein kinase A inhibitor N-[2-(p-Bromocinnamyla mino) ethyl]-5-isoquinoline sulfonamide (H-89). These results indicate that substance P induces adhesion of neutrophils to HUVEC by activation of prot ein kinase C via the NK1 receptor on the HUVEC.