The substance P(1-7) fragment is a potent modulator of substance P actions in the brain.
The neuropeptide, substance P (SP), produces a spectrum of behavioural effects. When given locally into the substantia nigra, SP induces dopamine release in the ipsilateral striatum and produces contralateral rotation in a dose-dependent, but bell-shaped, manner. Similar dose-response relationships have been observed for SP and other peptides in different bioassays. To test whether SP fragmentation is responsible for this phenomenon, SP(1-7), which is the main SP fragment in rat CNS, was injected intranigrally. SP(1-7) was found to act as a very potent antagonist against the SP-induced responses and was formed locally in the nigra after SP injection. It is proposed that SP(1-7) is an endogenous modulator of SP actions. Generation of peptide fragments, which retain receptor affinity but not efficacy, may be a general mechanism for autoregulation in peptidergic systems.
Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
M
M
Herrera-Marschitz
L
L
Terenius
T
T
Sakurada
M S
MS
Reid
U
U
Ungerstedt
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008845:Microinjections; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D010446:Peptide Fragments; D013373:Substance P; C036877:substance P (1-7)