Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1975 Apr;53(4):575–583. doi: 10.1111/j.1476-5381.1975.tb07397.x

Antagonism of adenosine 5'-triphosphate-induced relaxation by 2-2'-pyridylisatogen in the taenia of guinea-pig caecum.

M Spedding, A J Sweetman, D F Weetman
PMCID: PMC1666311  PMID: 1148500

Abstract

1. 2-2' Pyridylisatogen tosylate (PIT) (greater than 2.5 muM) relaxed the guinea-pig isolated taenia caeci by an unknown mechanism. 2. With higher concentrations of PIT (greater than 12.5 muM) subsequent applications of adenosine 5'-triphosphate (ATP) (2-600 muM) revealed a blockade of the ATP receptors. The antagonism was characterized by a delayed onset of action (greater than 10 min incubation with 50 muM PIT) and eventually became irreversible (greater than 50 muM PIT for greater than 30 minutes). The antagonism was specific for ATP, was not competitive, and was not dependent upon the relaxant effect. 3. The presence of either acetylcholine (0.05-1.0 muM) or carbachol (0.05-1.0 muM) increased the antagonistic effect of PIT (50 muM) approximately five-fold. 4. Following prolonged exposure, PIT (50 muM for 90 min) did not block the inhibitory effects of fiedl stimulation (2 Hz, 10 s) of the taenia caeci in the presence of hyoscine (0.33 muM). These results do not support the purinergic nerve hypothesis.

Full text

PDF
575

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. Beani L., Bianchi C., Crema A. Vagal non-adrenergic inhibition of guinea-pig stomach. J Physiol. 1971 Sep;217(2):259–279. doi: 10.1113/jphysiol.1971.sp009570. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bennett A., Posner J. Studies on prostaglandin antagonists. Br J Pharmacol. 1971 Aug;42(4):584–594. doi: 10.1111/j.1476-5381.1971.tb07142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bennett M. R., Burnstock G., Holman M. Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli. J Physiol. 1966 Feb;182(3):541–558. doi: 10.1113/jphysiol.1966.sp007836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bennett M. R., Rogers D. C. A study of the innervation of the taenia coli. J Cell Biol. 1967 Jun;33(3):573–596. doi: 10.1083/jcb.33.3.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bowman W. C., Hall M. T. Inhibition of rabbit intestine mediated by alpha- and beta-adrenoceptors. Br J Pharmacol. 1970 Feb;38(2):399–415. doi: 10.1111/j.1476-5381.1970.tb08528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bueding E., Bülbring E., Gercken G., Hawkins J. T., Kuriyama H. The effect of adrenaline on the adenosine otriphosphate and creatine phosphate content of intestinal smooth muscle. J Physiol. 1967 Nov;193(1):187–212. doi: 10.1113/jphysiol.1967.sp008351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Burnstock G., Campbell G., Rand M. J. The inhibitory innervation of the taenia of the guinea-pig caecum. J Physiol. 1966 Feb;182(3):504–526. doi: 10.1113/jphysiol.1966.sp007834. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Burnstock G., Campbell G., Satchell D., Smythe A. Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. Br J Pharmacol. 1970 Dec;40(4):668–688. doi: 10.1111/j.1476-5381.1970.tb10646.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  11. Campbell G. The inhibitory nerve fibres in the vagal supply to the guinea-pig stomach. J Physiol. 1966 Aug;185(3):600–612. doi: 10.1113/jphysiol.1966.sp008004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Furness J. B. An examination of nerve-mediated, hyoscine-resistant excitation of the guinea-pig colon. J Physiol. 1970 May;207(3):803–821. doi: 10.1113/jphysiol.1970.sp009096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. HIATT E. P. Sympatholytic effects of quinine and quinidine. Am J Physiol. 1950 Jan;160(1):212–216. doi: 10.1152/ajplegacy.1949.160.1.212. [DOI] [PubMed] [Google Scholar]
  14. Hooper M., Spedding M., Sweetman A. J., Weetman D. F. Proceedings: 2-2' pyridylisatogen tosylate: an antagonist of the inhibitory effects of ATP on smooth muscle. Br J Pharmacol. 1974 Mar;50(3):458P–459P. [PMC free article] [PubMed] [Google Scholar]
  15. MCEWEN L. M. The effect on the isolated rabbit heart of vagal stimulation and its modification by cocaine, hexamethonium and ouabain. J Physiol. 1956 Mar 28;131(3):678–689. doi: 10.1113/jphysiol.1956.sp005493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. McSwiney B. A., Robson J. M. The response of smooth muscle to stimulation of the vagus nerve. J Physiol. 1929 Oct 23;68(2):124–131. doi: 10.1113/jphysiol.1929.sp002599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. PATTERSON D. A., WIBBERLEY D. G. ISATOGENS. II. 2-2'-PYRIDYLISATOGEN. J Chem Soc. 1965 Mar;65:1706–1711. [PubMed] [Google Scholar]
  18. Rikimaru A., Fukushi Y., Suzuki T. Effects of imidazole and phentolamine on the relaxant responses of guinea-pig taenia coli to transmural stimulation and to adenosine triphosphate. Tohoku J Exp Med. 1971 Oct;105(2):199–200. doi: 10.1620/tjem.105.199. [DOI] [PubMed] [Google Scholar]
  19. STEPHENSON R. P. A modification of receptor theory. Br J Pharmacol Chemother. 1956 Dec;11(4):379–393. doi: 10.1111/j.1476-5381.1956.tb00006.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Satchell D., Burnstock G., Dann P. Antagonism of the effects of purinergic nerve stimulation and exogenously applied ATP on the guinea-pig taenia coli by 2-substituted imidazolines and related compounds. Eur J Pharmacol. 1973 Sep;23(3):264–269. doi: 10.1016/0014-2999(73)90093-9. [DOI] [PubMed] [Google Scholar]
  21. Schmid P. G., Nelson L. D., Mark A. L., Heistad D. D., Abboud F. M. Inhibition of adrenergic vasoconstriction by quinidine. J Pharmacol Exp Ther. 1974 Jan;188(1):124–134. [PubMed] [Google Scholar]
  22. Tomita T., Watanabe H. A comparison of the effects of adenosine triphosphate with noradrenaline and with the inhibitory potential of the guinea-pig taenia coli. J Physiol. 1973 May;231(1):167–177. doi: 10.1113/jphysiol.1973.sp010226. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. VAN ROSSUM J. M. Cumulative dose-response curves. II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters. Arch Int Pharmacodyn Ther. 1963;143:299–330. [PubMed] [Google Scholar]

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

RESOURCES