PMID: 7529387Aug 29, 1994Paper

An N-terminal fragment of substance P, substance P(1-7), down-regulates neurokinin-1 binding in the mouse spinal cord

Neuroscience Letters
Yukhananov RYu, A A Larson

Abstract

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...Continue Reading

References

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Citations

Jun 25, 1998·The American Journal of the Medical Sciences·I J Russell
Jul 19, 2002·Rheumatic Diseases Clinics of North America·I Jon Russell
Aug 23, 2000·Current Review of Pain·C L Rau, I J Russell
Nov 24, 1999·Baillière's Best Practice & Research. Clinical Rheumatology·I J Russell
Aug 10, 2002·The European Journal of Neuroscience·Rubén A VelázquezAlice A Larson
Nov 9, 2000·Clinical and Experimental Pharmacology & Physiology·S B Mazzone, D P Geraghty

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