Substance P and behavior: opposite effects of N-terminal and C-terminal fragments.

Most of the biological actions of substance P (SP) have been thought to be mediated by the carboxy-terminal portion of the peptide. Some of the behavioral effects produced by exogenous SP exhibit a strikingly different structure-activity relationship. The N-terminal heptapeptide fragment of SP, SP(1-7), inhibits nociceptive, aggressive and grooming behaviors and stimulates investigative motor behavior, but the C-terminal hexapeptide fragment analog pyroglutamyl-SP(7-11) exerts opposite effects. While the C-terminal fragment mimics the effects of administered intact SP on motor behaviors, the N-terminal fragment mimics the effects of intact SP on aggressive and nociceptive behaviors. The significant behavioral effects of SP(1-7) and the consistently opposite behavioral effects of N- and C-terminal fragments are important new findings.