Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Dec;113(4):1141–1146. doi: 10.1111/j.1476-5381.1994.tb17116.x

Effects of RP 67580, a tachykinin NK1 receptor antagonist, on a primary afferent-evoked response of ventral roots in the neonatal rat spinal cord.

R Hosoki 1, M Yanagisawa 1, J Z Guo 1, K Yoshioka 1, T Maehara 1, M Otsuka 1
PMCID: PMC1510513  PMID: 7534180

Abstract

1. The pharmacological characteristics of RP 67580, a non-peptide tachykinin NK1 receptor antagonist, and its effects on a reflex response evoked by stimulation of primary afferent fibres, were examined in isolated neonatal spinal cord preparations of the rat. Potentials were recorded extracellularly from a lumbar ventral root and drugs were bath-applied in normal artificial cerebrospinal fluid (CSF) or in the presence of tetrodotoxin (TTX). 2. In normal artificial CSF, RP 67580 (0.1-0.3 microM) caused rightward shifts of the concentration-response curves for substance P (SP), neurokinin A (NKA) and substance P methyl ester (SPOMe), an NK1-selective agonist, with pA2 values of 7.25, 7.47 and 7.49, respectively. 3. In the presence of TTX (0.3 microM), RP 67580 also caused rightward shifts of the concentration-response curves for SPOMe and NKA. The pA2 value of RP 67580 against SPOMe (6.75) was significantly lower than that against NKA (7.22). RP 67580 (0.3-1 microM) did not cause a clear parallel shift of the concentration-response curves for SP, and it depressed the depolarizations induced by low concentrations of SP, but slightly potentiated those induced by high concentrations of SP. 4. RP 67580 (1 microM) did not depress the depolarizing responses to bombesin, L--glutamate, gamma-aminobutyric acid (GABA), thyrotropin-releasing hormone and muscarine. RP 67580 (1 microM), however, depressed the response to acetylcholine in the presence of atropine and the response to nicotine. RP 68651 (1 microM), the enantiomer of RP 67580 devoid of activity at tachykinin NK1 receptors, also depressed the response to acetylcholine in the presence of atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
1141

Selected References

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

  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. Akagi H., Konishi S., Otsuka M., Yanagisawa M. The role of substance P as a neurotransmitter in the reflexes of slow time courses in the neonatal rat spinal cord. Br J Pharmacol. 1985 Mar;84(3):663–673. doi: 10.1111/j.1476-5381.1985.tb16148.x. [DOI] [PMC free article] [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. Beresford I. J., Birch P. J., Hagan R. M., Ireland S. J. Investigation into species variants in tachykinin NK1 receptors by use of the non-peptide antagonist, CP-96,345. Br J Pharmacol. 1991 Oct;104(2):292–293. doi: 10.1111/j.1476-5381.1991.tb12423.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chassaing G., Lavielle S., Brunissen A., Carruette A., Garret C., Petitet F., Saffroy M., Beaujouan J. C., Torrens Y., Glowinski J. [Pro9]SP and [pGlu6, Pro9]SP(6-11) interact with two different receptors in the guinea-pig ileum as demonstrated with new SP antagonists. Neuropeptides. 1992 Oct;23(2):73–79. doi: 10.1016/0143-4179(92)90081-7. [DOI] [PubMed] [Google Scholar]
  6. Fardin V., Foucault F., Bock M. D., Jolly A., Flamand O., Clerc F., Garret C. Variations in affinities for the NK1 receptor: differences between the non-peptide substance P antagonists RP 67580 and CP-96,345 and the agonist septide. Regul Pept. 1993 Jul 2;46(1-2):300–303. doi: 10.1016/0167-0115(93)90066-h. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Guo J. Z., Yoshioka K., Yanagisawa M., Hosoki R., Hagan R. M., Otsuka M. Depression of primary afferent-evoked responses by GR71251 in the isolated spinal cord of the neonatal rat. Br J Pharmacol. 1993 Nov;110(3):1142–1148. doi: 10.1111/j.1476-5381.1993.tb13933.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jahr C. E., Yoshioka K. Ia afferent excitation of motoneurones in the in vitro new-born rat spinal cord is selectively antagonized by kynurenate. J Physiol. 1986 Jan;370:515–530. doi: 10.1113/jphysiol.1986.sp015948. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kunitomo M., Imaizumi N., Sameshima E., Fujiwara M. Pharmacological analysis of receptors involved in the late, tachykininergic contractile response to electrical transmural stimulation in isolated rabbit iris sphincter muscle. Jpn J Pharmacol. 1993 Jul;62(3):257–261. doi: 10.1254/jjp.62.257. [DOI] [PubMed] [Google Scholar]
  12. Maggi C. A., Patacchini R., Meini S., Giuliani S. Evidence for the presence of a septide-sensitive tachykinin receptor in the circular muscle of the guinea-pig ileum. Eur J Pharmacol. 1993 Apr 28;235(2-3):309–311. doi: 10.1016/0014-2999(93)90152-8. [DOI] [PubMed] [Google Scholar]
  13. Nussbaumer J. C., Yanagisawa M., Otsuka M. Pharmacological properties of a C-fibre response evoked by saphenous nerve stimulation in an isolated spinal cord-nerve preparation of the newborn rat. Br J Pharmacol. 1989 Oct;98(2):373–382. doi: 10.1111/j.1476-5381.1989.tb12607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Otsuka M., Yanagisawa M. Effect of a tachykinin antagonist on a nociceptive reflex in the isolated spinal cord-tail preparation of the newborn rat. J Physiol. 1988 Jan;395:255–270. doi: 10.1113/jphysiol.1988.sp016917. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Otsuka M., Yoshioka K. Neurotransmitter functions of mammalian tachykinins. Physiol Rev. 1993 Apr;73(2):229–308. doi: 10.1152/physrev.1993.73.2.229. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Sakuma M., Yoshioka K., Suzuki H., Yanagisawa M., Onishi Y., Kobayashi N., Otsuka M. Substance P-evoked release of GABA from isolated spinal cord of the newborn rat. Neuroscience. 1991;45(2):323–330. doi: 10.1016/0306-4522(91)90229-h. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Surprenant A., North R. A., Katayama Y. Observations on the actions of substance P and [D-Arg1,D-Pro2,D-Trp7,9,Leu11)substance P on single neurons of the guinea pig submucous plexus. Neuroscience. 1987 Jan;20(1):189–199. doi: 10.1016/0306-4522(87)90011-x. [DOI] [PubMed] [Google Scholar]
  20. Watson S. P., Sandberg B. E., Hanley M. R., Iversen L. L. Tissue selectivity of substance P alkyl esters: suggesting multiple receptors. Eur J Pharmacol. 1983 Jan 28;87(1):77–84. doi: 10.1016/0014-2999(83)90052-3. [DOI] [PubMed] [Google Scholar]
  21. Yanagisawa M., Hosoki R., Otsuka M. The isolated spinal cord-skin preparation of the newborn rat and effects of some algogenic and analgesic substances. Eur J Pharmacol. 1992 Sep 22;220(2-3):111–117. doi: 10.1016/0014-2999(92)90737-o. [DOI] [PubMed] [Google Scholar]
  22. Yanagisawa M., Otsuka M., Konishi S., Akagi H., Folkers K., Rosell S. A substance P antagonist inhibits a slow reflex response in the spinal cord of the newborn rat. Acta Physiol Scand. 1982 Sep;116(1):109–112. doi: 10.1111/j.1748-1716.1982.tb10608.x. [DOI] [PubMed] [Google Scholar]
  23. Yanagisawa M., Otsuka M. Pharmacological profile of a tachykinin antagonist, spantide, as examined on rat spinal motoneurones. Br J Pharmacol. 1990 Aug;100(4):711–716. doi: 10.1111/j.1476-5381.1990.tb14080.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Yanagisawa M., Yoshioka K., Kurihara T., Saito K., Seno N., Suzuki H., Hosoki R., Otsuka M. Enzymatic inactivation of tachykinin neurotransmitters in the isolated spinal cord of the newborn rat. Neurosci Res. 1992 Dec;15(4):289–292. doi: 10.1016/0168-0102(92)90050-m. [DOI] [PubMed] [Google Scholar]
  25. Zhao F. Y., Saito K., Konishi S., Guo J. Z., Murakoshi T., Yoshioka K., Otsuka M. Involvement of NK1 receptors in synaptic transmission in the guinea pig coeliac ganglion. Neurosci Res. 1993 Dec;18(3):245–248. doi: 10.1016/0168-0102(93)90061-t. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES