A structure-activity profile of substance P and some of its fragments on supraspinal neurones in the rat.

Responses of neurones in the cingulate cortex to iontophoretically applied substance P (SP) were compared to its various C-terminal fragments. Fragments as short as the hexapeptide sequence were at least as active in increasing neuronal firing as the parent molecule. The pentapeptide sequence was much less active and the tripeptide sequence inactive. Compared on a current basis the octa-, hepta- and hexapeptides all evoked larger responses than the full sequence SP. In addition, the nonapeptide N-terminal sequence of SP had no effect on any neurone on which it was tested.