Investigation of the metabolism of substance P at the blood-brain barrier using capillary electrophoresis with laser-induced fluorescence detection.

Substance P (SP) metabolism was investigated upon exposure to a monolayer of bovine brain microvessel endothelial cells (BBMECs), a cell culture model of the blood-brain barrier. SP was incubated with the BBMECs and its metabolism was followed as a function of time over a 5-h period. The resulting samples were derivatized with naphthalene-2,3-dicarboxaldehyde (NDA)/cyanide, separated, and detected using cyclodextrin-modified electrokinetic chromatography with laser-induced fluorescence detection (CDMEKC-LIF). Upon exposure to the BBMEC monolayer, SP rapidly degraded to produce the N-terminal (1-9), (1-4) and (1-7) and C-terminal (2-11) and (3-11) fragments. These results were compared with those in an earlier report from our laboratory, where SP metabolism was investigated in vivo by microdialysis sampling in rat striatum.