Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 318, Issue 4, pp 281–287 | Cite as

The possible existence of multiple receptors for substance P

  • Chi-Ming Lee
  • Leslie L. Iversen
  • Michael R. Hanley
  • Bengt E. B. Sandberg
Article

Summary

  1. 1.

    The possible existence of multiple receptors for substance P (SP) was investigated by examining the relative pharmacological potencies of SP and related peptides in contracting guinea pig ileum, in potentiating electrically evoked contractions of rat vas deferens preparations and in competing for 3H-SP receptor binding in rat brain membranes, and by comparing the extent of cross-tachyphylaxis of various analogues with SP in the guinea pig ileum.

     
  2. 2.

    Different rank orders of potencies were observed among SP, its C-terminal fragments, analogues and related tachykinins in the different test systems, and these could not be explained by differential access to the target organ receptors.

     
  3. 3.

    In contrast to SP and physalaemin, both eledoisin and a metabolically stable SP analogue, [pGlu5, MePhe8, Sar9]-SP5-11 exhibited differential recovery from SP tachyphylaxis in the guinea pig ileum, and part of their spasmogenic action in this preparation was atropine-sensitive.

     
  4. 4.

    The results suggest the possible existence of multiple SP receptors, and the specificity of those in the brain may be different from those in the gut. The structural and pharmacological basis for subdividing tachykinins into SP-physalaemin and eledoisin-kassinin families is also discussed.

     

Key words

Substance P Tachykinin Tachyphylaxis Structure-activity relationship Multiple receptors 

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Copyright information

© Springer-Verlag 1982

Authors and Affiliations

  • Chi-Ming Lee
    • 1
  • Leslie L. Iversen
    • 1
  • Michael R. Hanley
    • 1
  • Bengt E. B. Sandberg
    • 1
  1. 1.MRC Neurochemical Pharmacology Unit, Medical Research Council CentreMedical SchoolCambridgeUK

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