An N-terminal fragment of substance P, substance P(1-7), down-regulates neurokinin-1 binding in the mouse spinal cord.
Injected intrathecally, substance P (SP) down-regulates neurokinin-1 (NK-1) binding in the spinal cord and desensitizes rats to the behavioral effect of SP. N-terminal fragments of SP, such as SP(1-7), induce antinociception and play a role in desensitization to SP in mice. The goal of this study was to assess the abilities of N- and C-terminal fragments of SP to down-regulate NK-1 binding. Binding of [3H]SP to mouse spinal cord membranes was inhibited by SP, CP-96,345, and to a lesser extent by SP(5-11), but not SP(1-7), consistent with these binding sites being NK-1 receptors. Injection of SP(5-11) intrathecally did not affect the affinity (Kd) or concentration (Bmax) of [3H]SP binding. However, injection of 1 nmol of SP(1-7) decreased the Bmax of [3H]SP binding in the spinal cord at 6 h after its injection just as this dose of SP decreased the Bmax at 24 h. These data suggest that the N-terminus of SP is responsible for down-regulation of NK-1 binding. As SP(5-11) did not down-regulate NK-1 binding, activation of NK-1 sites does not appear necessary or sufficient for down-regulation of SP binding. In contrast, SP(1-7), in spite of its inability to interact with NK-1 sites, did down-regulate SP binding, suggesting an indirect mechanism dissociated from NK-1 receptors.
Yukhananov RYu
Department of Cell Biology, Neurobiology and Anatomy, Loyola University Stritch School of Medicine, Maywood, IL 60153.
Larson
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AA
D000818:Animals; D015536:Down-Regulation; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology; D018040:Receptors, Neurokinin-1 / Q000187:drug effects / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D014316:Tritium
D010446:Peptide Fragments; D018040:Receptors, Neurokinin-1; D014316:Tritium; D013373:Substance P; C031661:substance P (5-11); C036877:substance P (1-7)