Modulation of isolation-induced fighting by N- and C-terminal analogs of substance P: evidence for multiple recognition sites.
Substance P (SP) significantly reduced fighting in mice made aggressive by prolonged isolation. The N-terminal heptapeptide fragment SP (1-7) also reduced fighting. The C-terminal fragment SP(4-11) was without activity, while the shorter C-terminal fragment analog less than E-SP(7-11) significantly increased isolation-induced fighting. The aggression-enhancing effect of less than E-SP(7-11) was antagonized by naloxone, which by itself had no significant effect. The aggression-reducing effect of SP(1-11) was significantly enhanced by naloxone, while the effect of SP(1-7) was unchanged. These results demonstrate that a behavioral effect of SP may be duplicated by an N-terminal fragment of the SP molecule, and that peptide fragments or analogs of the N- and C-terminal portions of the SP molecule can exert opposing effects on a specific behavior. These findings represent a structure/activity relationship that is strikingly different from any previously described for SP. The differing effects of naloxone on N- and C-terminal fragment analogs suggest that these two effects may be mediated by different mechanisms.
D000374:Aggression / Q000187:drug effects*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D011956:Receptors, Cell Surface / Q000502:physiology; D018040:Receptors, Neurokinin-1; D012934:Social Isolation; D013329:Structure-Activity Relationship; D013373:Substance P / Q000031:analogs & derivatives* / Q000494:pharmacology*
D009842:Oligopeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018040:Receptors, Neurokinin-1; D013373:Substance P; D009270:Naloxone; C032682:substance P (4-11); C026238:substance P (6-11), pGlu(6)-; C036877:substance P (1-7); D011761:Pyrrolidonecarboxylic Acid