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. 1982 Feb;75(2):341–351. doi: 10.1111/j.1476-5381.1982.tb08792.x

Relative activities of substance P-related peptides in the guinea-pig ileum and rat parotid gland, in vitro.

P R Gater, C C Jordan, D G Owen
PMCID: PMC2071613  PMID: 6194840

Abstract

The relative potencies of a series of substance P analogues have been determined for spasmogenic activity in the guinea-pig ileum in vitro and for the release of 86Rb and alpha-amylase activity from rat parotid gland slices in vitro. Equipotent molar ratios (EMR), relative to substance P, were determined for all the compounds. In the rat parotid gland, EC50 values for amylase release were, on average, 35.5 times greater than those for 86Rb release. Analysis of Hill plots suggests that spare receptors exist for 86Rb release but not for amylase release and it is suggested that the stimulus-response coupling for amylase release may be less efficient than that for 86Rb release. In the parotid gland, the octapeptide and [less than Glu6]-hexapeptide C-terminal fragments of substance P were less active than substance P itself, whereas in the ileum, the octapeptide was as active as substance P. Substitutions at the Phe7 or Phe8 positions in general reduced activity relative to substance P. This effect was particularly apparent in C-terminal hexapeptide analogues. Substitutions at the Phe7 and Phe8 positions in C-terminal hexapeptide analogues produced a greater reduction in activity in the parotid gland than in the ileum. The most marked difference was observed with eledoisin-related peptide for which the ratio of EMRs for ileum and 86Rb release was 18.1. The unsubstituted C-terminal octapeptide fragment similarly showed a discrepancy between the two assay systems (EMR ratio, ileum: 86Rb release = 7.75). It is suggested that the results may indicate the presence of sub-populations of 'substance P receptors' which are represented at least in different proportions in the two tissues studied, although alternative explanations such as differences in metabolism of agonists are possible.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Batzri S., Selinger Z., Schramm M., Robinovitch M. R. Potassium release mediated by the epinephrine -receptor in rat parotid slices. Properties and relation to enzyme secretion. J Biol Chem. 1973 Jan 10;248(1):361–368. [PubMed] [Google Scholar]
  2. Bury R. W., Mashford M. L. Biological activity of C-terminal partial sequences of substance P. J Med Chem. 1976 Jun;19(6):854–856. doi: 10.1021/jm00228a028. [DOI] [PubMed] [Google Scholar]
  3. Carlsö B., Danielsson A., Henriksson R., Idahl L. A. Characterization of the rat parotid beta-adrenoceptor. Br J Pharmacol. 1981 Feb;72(2):271–276. doi: 10.1111/j.1476-5381.1981.tb09124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Chipkin R. E., Stewart J. M., Sweeney V. E., Harris K., Williams R. In vitro activities of some synthetic substance P analogs. Arch Int Pharmacodyn Ther. 1979 Aug;240(2):193–202. [PubMed] [Google Scholar]
  5. Cutting D. A., Jordan C. C. Alternative approaches to analgesia: baclofen as a model compound. Br J Pharmacol. 1975 Jun;54(2):171–179. doi: 10.1111/j.1476-5381.1975.tb06926.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Friedman Z. Y., Selinger Z. A transient release of potassium mediated by the action of substance P on rat parotid slices. J Physiol. 1978 May;278:461–469. doi: 10.1113/jphysiol.1978.sp012317. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hanley M. R., Lee C. M., Michell R. H., Jones L. M. Similar effects of substance P and related peptides on salivation and on phosphatidylinositol turnover in rat salivary glands. Mol Pharmacol. 1980 Jul;18(1):78–83. [PubMed] [Google Scholar]
  8. Hanley M. R., Sandberg B. E., Lee C. M., Iversen L. L., Brundish D. E., Wade R. Specific binding of 3H-substance P to rat brain membranes. Nature. 1980 Aug 21;286(5775):810–812. doi: 10.1038/286810a0. [DOI] [PubMed] [Google Scholar]
  9. Hökfelt T., Ljungdahl A., Terenius L., Elde R., Nilsson G. Immunohistochemical analysis of peptide pathways possibly related to pain and analgesia: enkephalin and substance P. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3081–3085. doi: 10.1073/pnas.74.7.3081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Leban J., Rackur G., Yamaguchi I., Folkers K., Björkroth U., Rosell S., Yanaihara N., Yanaihara C. Synthesis of substance P analogs and agonistic and antagonistic activities. Acta Chem Scand B. 1979;33(9):664–668. doi: 10.3891/acta.chem.scand.33b-0664. [DOI] [PubMed] [Google Scholar]
  11. Leslie B. A., Putney J. W., Jr, Sherman J. M. alpha-Adrenergic, beta-adrenergic and cholinergic mechanisms for amylase secretion by rat parotid gland in vitro. J Physiol. 1976 Sep;260(2):351–370. doi: 10.1113/jphysiol.1976.sp011519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Putney J. W., Jr Biphasic modulation of potassium release in rat parotid gland by carbachol and phenylephrine. J Pharmacol Exp Ther. 1976 Aug;198(2):375–384. [PubMed] [Google Scholar]
  13. Putney J. W., Jr Muscarinic, alpha-adrenergic and peptide receptors regulate the same calcium influx sites in the parotid gland. J Physiol. 1977 Jun;268(1):139–149. doi: 10.1113/jphysiol.1977.sp011851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Putney J. W., Jr, Van de Walle C. M., Wheeler C. S. Binding of 125I-physalaemin to rat parotid acinar cells. J Physiol. 1980 Apr;301:205–212. doi: 10.1113/jphysiol.1980.sp013199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rudich L., Butcher F. R. Effect of substance P and eledoisin on K+ efflux, amylase release and cyclic nucleotide levels in slices of rat parotid gland. Biochim Biophys Acta. 1976 Oct 22;444(3):704–711. doi: 10.1016/0304-4165(76)90317-2. [DOI] [PubMed] [Google Scholar]
  16. Schild H. O. A method of conducting a biological assay on a preparation giving repeated graded responses illustrated by the estimation of histamine. J Physiol. 1942 Jun 2;101(1):115–130. doi: 10.1113/jphysiol.1942.sp003970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Teichberg V. I., Cohen S., Blumberg S. Distinct classes of substance P receptors revealed by a comparison of the activities of substance P and some of its segments. Regul Pept. 1981 Feb;1(5):327–333. doi: 10.1016/0167-0115(81)90056-2. [DOI] [PubMed] [Google Scholar]
  18. Templeton D. Augmented amylase release from rat parotid gland slices, in vitro. Pflugers Arch. 1980 Apr;384(3):287–289. doi: 10.1007/BF00584564. [DOI] [PubMed] [Google Scholar]

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