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. 1994 Mar;111(3):739–746. doi: 10.1111/j.1476-5381.1994.tb14800.x

Tachykinin NK1 receptor subtypes in the rat urinary bladder.

S Meini 1, R Patacchini 1, C A Maggi 1
PMCID: PMC1910071  PMID: 7517327

Abstract

1. Following the recent proposal that the selective agonist septide, ([pGlu6,Pro9]SP(6-11)), acts on a novel tachykinin receptor distinct from the 'classical' NK1 receptor, the aim of the study was to investigate the possible heterogeneity of tachykinin NK1 receptors in the rat urinary bladder. 2. The synthetic tachykinin receptor agonists, septide (pD2 7.87) and [Sar9]substance P (SP) sulphone (pD2 7.64) produced concentration-dependent contractions of the rat isolated urinary bladder. 3. The NK1 receptor antagonists GR82,334, (+/-)-CP96,345, and RP67,580 competitively antagonized (slopes of Schild plot not significantly different from unity) the response to septide with the rank order of potency (pKB values in parentheses): RP 67,580 (7.57) > GR 82,334 (7.01) > (+/-)-CP 96,345 (6.80). The same antagonists were significantly less potent when tested against [Sar9]SP sulphone, while maintaining the same rank order of potency: RP 67,580 (7.00) > GR 82,334 (5.93) > (+/-)-CP 96,345 (< 6). The antagonists did not affect the concentration-response curve to bombesin. 4. To exclude the involvement of the NK2 receptor, a second series of experiments was performed in the presence of the potent nonpeptide NK2 receptor antagonist, SR 48,968. SR 48,968 (1 microM) produced a rightward shift of the concentration-response curve to the NK2 receptor selective agonist, [beta Ala8]neurokinin A (NKA) (4-10). SR 48,968 did not significantly modify the response to SP, NKA, neurokinin B (NKB), neuropeptide K (NPK), neuropeptide gamma (NP gamma), SP(4-11), SP(6-11), septide or [Sar9]SP sulphone.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Advenier C., Rouissi N., Nguyen Q. T., Emonds-Alt X., Breliere J. C., Neliat G., Naline E., Regoli D. Neurokinin A (NK2) receptor revisited with SR 48968, a potent non-peptide antagonist. Biochem Biophys Res Commun. 1992 May 15;184(3):1418–1424. doi: 10.1016/s0006-291x(05)80041-5. [DOI] [PubMed] [Google Scholar]
  3. Barr A. J., Watson S. P. Non-peptide antagonists, CP-96,345 and RP 67580, distinguish species variants in tachykinin NK1 receptors. Br J Pharmacol. 1993 Jan;108(1):223–227. doi: 10.1111/j.1476-5381.1993.tb13466.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burcher E., Buck S. H. Multiple tachykinin binding sites in hamster, rat and guinea-pig urinary bladder. Eur J Pharmacol. 1986 Sep 9;128(3):165–177. doi: 10.1016/0014-2999(86)90763-6. [DOI] [PubMed] [Google Scholar]
  5. Dion S., D'Orléans-Juste P., Drapeau G., Rhaleb N. E., Rouissi N., Tousignant C., Regoli D. Characterization of neurokinin receptors in various isolated organs by the use of selective agonists. Life Sci. 1987 Nov 16;41(20):2269–2278. doi: 10.1016/0024-3205(87)90538-8. [DOI] [PubMed] [Google Scholar]
  6. Fong T. M., Huang R. R., Strader C. D. Localization of agonist and antagonist binding domains of the human neurokinin-1 receptor. J Biol Chem. 1992 Dec 25;267(36):25664–25667. [PubMed] [Google Scholar]
  7. Fong T. M., Yu H., Huang R. R., Strader C. D. The extracellular domain of the neurokinin-1 receptor is required for high-affinity binding of peptides. Biochemistry. 1992 Dec 1;31(47):11806–11811. doi: 10.1021/bi00162a019. [DOI] [PubMed] [Google Scholar]
  8. Fong T. M., Yu H., Strader C. D. Molecular basis for the species selectivity of the neurokinin-1 receptor antagonists CP-96,345 and RP67580. J Biol Chem. 1992 Dec 25;267(36):25668–25671. [PubMed] [Google Scholar]
  9. Garret C., Carruette A., Fardin V., Moussaoui S., Peyronel J. F., Blanchard J. C., Laduron P. M. Pharmacological properties of a potent and selective nonpeptide substance P antagonist. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):10208–10212. doi: 10.1073/pnas.88.22.10208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gerard N. P., Bao L., Xiao-Ping H., Gerard C. Molecular aspects of the tachykinin receptors. Regul Pept. 1993 Jan 22;43(1-2):21–35. doi: 10.1016/0167-0115(93)90404-v. [DOI] [PubMed] [Google Scholar]
  11. Gitter B. D., Waters D. C., Bruns R. F., Mason N. R., Nixon J. A., Howbert J. J. Species differences in affinities of non-peptide antagonists for substance P receptors. Eur J Pharmacol. 1991 May 17;197(2-3):237–238. doi: 10.1016/0014-2999(91)90532-u. [DOI] [PubMed] [Google Scholar]
  12. Hall J. M., Flowers J. M., Morton I. K. A pharmacological study of NK1 and NK2 tachykinin receptor characteristics in the rat isolated urinary bladder. Br J Pharmacol. 1992 Nov;107(3):777–784. doi: 10.1111/j.1476-5381.1992.tb14523.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hall J. M., Morton I. K. Novel selective agonists and antagonists confirm neurokinin NK1 receptors in guinea-pig vas deferens. Br J Pharmacol. 1991 Feb;102(2):511–517. doi: 10.1111/j.1476-5381.1991.tb12202.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Jenkinson D. H. How we describe competitive antagonists: three questions of usage. Trends Pharmacol Sci. 1991 Feb;12(2):53–54. doi: 10.1016/0165-6147(91)90497-g. [DOI] [PubMed] [Google Scholar]
  15. Kage R., Leeman S. E., Boyd N. D. Biochemical characterization of two different forms of the substance P receptor in rat submaxillary gland. J Neurochem. 1993 Jan;60(1):347–351. doi: 10.1111/j.1471-4159.1993.tb05857.x. [DOI] [PubMed] [Google Scholar]
  16. Kenakin T. P. The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev. 1984 Sep;36(3):165–222. [PubMed] [Google Scholar]
  17. Laufer R., Gilon C., Chorev M., Selinger Z. Desensitization with a selective agonist discriminates between multiple tachykinin receptors. J Pharmacol Exp Ther. 1988 May;245(2):639–643. [PubMed] [Google Scholar]
  18. Lee C. M., Campbell N. J., Williams B. J., Iversen L. L. Multiple tachykinin binding sites in peripheral tissues and in brain. Eur J Pharmacol. 1986 Nov 4;130(3):209–217. doi: 10.1016/0014-2999(86)90270-0. [DOI] [PubMed] [Google Scholar]
  19. Maggi C. A., Coy D. H., Giuliani S. Effect of [D-Phe6] bombesin (6-13) methylester, a bombesin receptor antagonist, towards bombesin-induced contractions in the guinea-pig and rat isolated urinary bladder. J Auton Pharmacol. 1992 Aug;12(4):215–222. doi: 10.1111/j.1474-8673.1992.tb00335.x. [DOI] [PubMed] [Google Scholar]
  20. Maggi C. A., Parlani M., Astolfi M., Santicioli P., Rovero P., Abelli L., Somma V., Giuliani S., Regoli D., Patacchini R. Neurokinin receptors in the rat lower urinary tract. J Pharmacol Exp Ther. 1988 Jul;246(1):308–315. [PubMed] [Google Scholar]
  21. Maggi C. A., Patacchini R., Giuliani S., Giachetti A. In vivo and in vitro pharmacology of SR 48,968, a non-peptide tachykinin NK2 receptor antagonist. Eur J Pharmacol. 1993 Mar 30;234(1):83–90. doi: 10.1016/0014-2999(93)90709-q. [DOI] [PubMed] [Google Scholar]
  22. Maggi C. A., Patacchini R., Quartara L., Rovero P., Santicioli P. Tachykinin receptors in the guinea-pig isolated bronchi. Eur J Pharmacol. 1991 May 17;197(2-3):167–174. doi: 10.1016/0014-2999(91)90517-t. [DOI] [PubMed] [Google Scholar]
  23. Patacchini R., Santicioli P., Astolfi M., Rovero P., Viti G., Maggi C. A. Activity of peptide and non-peptide antagonists at peripheral NK1 receptors. Eur J Pharmacol. 1992 Apr 29;215(1):93–98. doi: 10.1016/0014-2999(92)90613-9. [DOI] [PubMed] [Google Scholar]
  24. Petitet F., Saffroy M., Torrens Y., Lavielle S., Chassaing G., Loeuillet D., Glowinski J., Beaujouan J. C. Possible existence of a new tachykinin receptor subtype in the guinea pig ileum. Peptides. 1992 Mar-Apr;13(2):383–388. doi: 10.1016/0196-9781(92)90125-m. [DOI] [PubMed] [Google Scholar]
  25. Snider R. M., Constantine J. W., Lowe J. A., 3rd, Longo K. P., Lebel W. S., Woody H. A., Drozda S. E., Desai M. C., Vinick F. J., Spencer R. W. A potent nonpeptide antagonist of the substance P (NK1) receptor. Science. 1991 Jan 25;251(4992):435–437. doi: 10.1126/science.1703323. [DOI] [PubMed] [Google Scholar]
  26. Takeda Y., Krause J. E. Neuropeptide K potently stimulates salivary gland secretion and potentiates substance P-induced salivation. Proc Natl Acad Sci U S A. 1989 Jan;86(1):392–396. doi: 10.1073/pnas.86.1.392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Takeda Y., Krause J. E. gamma-Preprotachykinin-(72-92)-peptide amide potentiates substance P-induced salivation. Eur J Pharmacol. 1989 Feb 28;161(2-3):267–271. doi: 10.1016/0014-2999(89)90858-3. [DOI] [PubMed] [Google Scholar]
  28. Tousignant C., Guillemette G., Regoli D. Binding sites for [3H][Sar9, Met(O2)11]substance P in rat brain and guinea pig ileum. Brain Res. 1991 Sep 27;560(1-2):1–11. doi: 10.1016/0006-8993(91)91207-h. [DOI] [PubMed] [Google Scholar]
  29. Ward P., Ewan G. B., Jordan C. C., Ireland S. J., Hagan R. M., Brown J. R. Potent and highly selective neurokinin antagonists. J Med Chem. 1990 Jul;33(7):1848–1851. doi: 10.1021/jm00169a003. [DOI] [PubMed] [Google Scholar]
  30. Wormser U., Laufer R., Hart Y., Chorev M., Gilon C., Selinger Z. Highly selective agonists for substance P receptor subtypes. EMBO J. 1986 Nov;5(11):2805–2808. doi: 10.1002/j.1460-2075.1986.tb04571.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. van Giersbergen P. L., Shatzer S. A., Burcher E., Buck S. H. Comparison of the effects of neuropeptide K and neuropeptide gamma with neurokinin A at NK2 receptors in the hamster urinary bladder. Naunyn Schmiedebergs Arch Pharmacol. 1992 Jan;345(1):51–56. doi: 10.1007/BF00175469. [DOI] [PubMed] [Google Scholar]

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