Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1984 Sep;83(1):169–177. doi: 10.1111/j.1476-5381.1984.tb10132.x

Evidence that ethylenediamine acts in the isolated ileum of the guinea-pig by releasing endogenous GABA.

D I Kerr, J Ong
PMCID: PMC1987199  PMID: 6487887

Abstract

Ethylenediamine (EDA) released [3H]-gamma-aminobutyric acid ([3H]-GABA) in a dose-dependent manner from the isolated preloaded ileum of the guinea-pig maintained in Krebs-bicarbonate solution (pH 7.4, 37 degrees C), in the presence of beta-alanine and amino-oxyacetic acid (AOAA) to prevent GABA uptake into glial cells and catabolism. This release was reversibly prevented by 3-mercaptopropionic acid (3-MPA), also in a dose-dependent manner. In the isolated ileal preparations of the guinea-pig maintained in Krebs-bicarbonate solution, EDA induced a dose-dependent transient, cholinergic contractile response (GABAA-receptor-mediated effect), followed by an 'after-relaxation' (GABAB-receptor-mediated effect). EDA also induced a transient contraction superimposed on repetitive twitch responses to electrical transmural stimulation of the cholinergic neurones, followed by a depression of the twitch contractions. This GABAA-receptor-mediated contraction was antagonized by bicuculline methochloride and picrotoxinin, whilst the GABAB-receptor-mediated 'after-relaxation', and depression of cholinergic twitch contractions, was susceptible to antagonism by delta-aminovaleric acid. The pA2 value for bicuculline methochloride antagonism of EDA was estimated to be 5.8, identical with that for GABA. 3-Mercaptopropionic acid also prevented these pharmacological actions induced by EDA without affecting responses to GABA, 3-aminopropranesulphonic acid, muscimol, baclofen or the twitch responses to transmural stimulation. It is concluded that EDA releases both [3H]-GABA and endogenous GABA in the guinea-pig ileum, thus providing further evidence that GABA is a transmitter in the enteric nervous system.

Full text

PDF
169

Selected References

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

  1. Bowery N. G., Doble A., Hill D. R., Hudson A. L., Shaw J. S., Turnbull M. J., Warrington R. Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol. 1981 Apr 24;71(1):53–70. doi: 10.1016/0014-2999(81)90386-1. [DOI] [PubMed] [Google Scholar]
  2. Fan S. G., Wusteman M., Iversen L. L. 3-mercaptopropionic acid inhibits GABA release from rat brain slices in vitro. Brain Res. 1981 Dec 21;229(2):371–377. doi: 10.1016/0006-8993(81)91001-5. [DOI] [PubMed] [Google Scholar]
  3. Giotti A., Luzzi S., Spagnesi S., Zilletti L. GABAA and GABAB receptor-mediated effects in guinea-pig ileum. Br J Pharmacol. 1983 Mar;78(3):469–478. doi: 10.1111/j.1476-5381.1983.tb08807.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Jessen K. R., Hills J. M., Dennison M. E., Mirsky R. Gamma-aminobutyrate as an autonomic neurotransmitter: release and uptake of [3H]gamma-aminobutyrate in guinea pig large intestine and cultured enteric neurons using physiological methods and electron microscopic autoradiography. Neuroscience. 1983 Dec;10(4):1427–1442. doi: 10.1016/0306-4522(83)90124-0. [DOI] [PubMed] [Google Scholar]
  5. Jessen K. R., Mirsky R., Dennison M. E., Burnstock G. GABA may be a neurotransmitter in the vertebrate peripheral nervous system. Nature. 1979 Sep 6;281(5726):71–74. doi: 10.1038/281071a0. [DOI] [PubMed] [Google Scholar]
  6. Kaplita P. V., Waters D. H., Triggle D. J. gamma-Aminobutyric acid action in guinea-pig ileal myenteric plexus. Eur J Pharmacol. 1982 Apr 8;79(1-2):43–51. doi: 10.1016/0014-2999(82)90573-8. [DOI] [PubMed] [Google Scholar]
  7. Karlsson A., Fonnum F., Malthe-Sorenssen D., Storm-Mathisen J. Effect of the convulsive agent 3-mercaptopropionic acid on the levels of GABA, other amino acids and glutamate decarboxylase in different regions of the rat brain. Biochem Pharmacol. 1974 Nov 1;23(21):3053–3061. doi: 10.1016/0006-2952(74)90281-0. [DOI] [PubMed] [Google Scholar]
  8. Kerr D. I., Krantis A. Uptake and stimulus-evoked release of [3H]-gamma-aminobutyric acid by myenteric nerves of guinea-pig intestine. Br J Pharmacol. 1983 Feb;78(2):271–276. doi: 10.1111/j.1476-5381.1983.tb09391.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Krantis A., Kerr D. I. Autoradiographic localization of [3H]gamma-amino-butyric acid in the myenteric plexus of the guinea-pig small intestine. Neurosci Lett. 1981 May 29;23(3):263–268. doi: 10.1016/0304-3940(81)90008-2. [DOI] [PubMed] [Google Scholar]
  10. Krantis A., Kerr D. I. Gaba induced excitatory responses in the guinea-pig small intestine are antagonized by bicuculline, picrotoxinin and chloride ion blockers. Naunyn Schmiedebergs Arch Pharmacol. 1981 Nov;317(3):257–261. doi: 10.1007/BF00503827. [DOI] [PubMed] [Google Scholar]
  11. Krantis A., Kerr D. I. The effect of GABA antagonism on propulsive activity of the guinea-pig large intestine. Eur J Pharmacol. 1981 Nov 19;76(1):111–114. doi: 10.1016/0014-2999(81)90018-2. [DOI] [PubMed] [Google Scholar]
  12. Lamar C., Jr Mercaptopropionic acid: a convulsant that inhibits glutamate decarboxylase. J Neurochem. 1970 Feb;17(2):165–170. doi: 10.1111/j.1471-4159.1970.tb02197.x. [DOI] [PubMed] [Google Scholar]
  13. Lloyd H. G., Perkins M. N., Stone T. W. Ethylenediamine as a specific releasing agent of gamma-aminobutyric acid in rat striatal slices. J Neurochem. 1982 Apr;38(4):1168–1169. doi: 10.1111/j.1471-4159.1982.tb05366.x. [DOI] [PubMed] [Google Scholar]
  14. Meldrum B. Pharmacology of GABA. Clin Neuropharmacol. 1982;5(3):293–316. doi: 10.1097/00002826-198205030-00004. [DOI] [PubMed] [Google Scholar]
  15. Miki Y., Taniyama K., Tanaka C., Tobe T. GABA, glutamic acid decarboxylase, and GABA transaminase levels in the myenteric plexus in the intestine of humans and other mammals. J Neurochem. 1983 Mar;40(3):861–865. doi: 10.1111/j.1471-4159.1983.tb08059.x. [DOI] [PubMed] [Google Scholar]
  16. Muhyaddin M., Roberts P. J., Woodruff G. N. Presynaptic gamma-aminobutyric acid receptors in the rat anococcygeus muscle and their antagonism by 5-aminovaleric acid. Br J Pharmacol. 1982 Sep;77(1):163–168. doi: 10.1111/j.1476-5381.1982.tb09282.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ong J., Kerr D. I. GABAA- and GABAB-receptor-mediated modification of intestinal motility. Eur J Pharmacol. 1982 Dec 17;86(1):9–17. doi: 10.1016/0014-2999(82)90390-9. [DOI] [PubMed] [Google Scholar]
  18. Perkins M. N., Bowery N. G., Hill D. R., Stone T. W. Neuronal responses to ethylenediamine: preferential blockade by bicuculline. Neurosci Lett. 1981 May 29;23(3):325–327. doi: 10.1016/0304-3940(81)90019-7. [DOI] [PubMed] [Google Scholar]
  19. Taniyama K., Kusunoki M., Saito N., Tanaka C. [Release of gamma-aminobutyric acid from cat colon]. Science. 1982 Sep 10;217(4564):1038–1040. doi: 10.1126/science.7112110. [DOI] [PubMed] [Google Scholar]

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

RESOURCES