Structure-Activity Relationships of Agonist and Antagonist Ligands

  • Scott L. Harbeson
  • Paolo Rovero
Part of the The Receptors book series (REC)

Abstract

The biological activity of substance P (SP) C-terminal partial sequences has been previously reported (Bury and Mashford, 1976). The minimum sequence that maintains significant biological activity in the isolated guinea pig ileum is the pentapeptide, SP7–11. This concept has been recently confirmed by binding experiments to cloned rat NK1, NK2, and NK3 receptors heterologously expressed in Chinese hamster ovary cells (Cascieri et al., 1992). C-terminal partial sequences of SP, neurokinin A (NKA), and neurokinin B (NKB) have also been tested on monoreceptorial prepa-rations selective for each of the three tachykinin receptor types (Dion et al., 1987b). The results obtained with SP and its fragments on the isolated dog carotid artery clearly indicate that, at the NK1 receptor, SP is more potent than its fragments, although these fragments maintain full agonist activity. Since some of the C-terminal fragments of NKA are more active than NKA itself at the NK2 receptor (see Section 2.1.1.), the activity of the fragments has been used as a second criterion for the classification of the tachykinin receptors, in addition to the rank order of potency of natural ligands (Regoli et al., 1987). Thus, the three tachykinin receptor types are defined as follows:
  1. NK1

    SP > NKA and > NKB.

    The tachykinins are more active than their respective fragments.

     
  2. NK2

    NKA > NKB > SP.

    Some NKA fragments are more selective than their precursor.

     
  3. NK3

    NKB > NKA > SP.

    Fragments of NKB are less active than their precursor.

     

Keywords

Amide Disulfide Leucine Amylase Propyl 

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© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Scott L. Harbeson
  • Paolo Rovero

There are no affiliations available

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