Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Dec;107(4):919–923. doi: 10.1111/j.1476-5381.1992.tb13386.x

Histamine H3 receptors modulate the release of [3H]-acetylcholine from slices of rat entorhinal cortex: evidence for the possible existence of H3 receptor subtypes.

J Clapham 1, G J Kilpatrick 1
PMCID: PMC1907926  PMID: 1334753

Abstract

1. The effect of agents which interact with the histamine H3 receptor on potassium-stimulated tritium release from slices of rat entorhinal cortex preloaded with [3H]-choline is described. We have examined the effects of the selective H3 receptor agonist, (R)-alpha-methylhistamine (RAMH), and a number of H3 receptor antagonists, including the selective compound thioperamide, on the potassium-stimulated release of tritium. 2. In the presence of mepyramine and ranitidine, RAMH (0.01-10 microM) inhibited potassium-stimulated tritium release in a concentration-dependent manner, EC50 = 0.11 microM. The maximum inhibition was approximately 50%. 3. Thioperamide displaced the RAMH concentration-response curve to the right yielding a pKB value of 8.4. There was no change in the maximum response to RAMH. 4. Other H3 receptor antagonists, including impromidine and burimamide, also caused rightwards displacement of the linear portion of the RAMH concentration-response curve. However, phenylbutanoylhistamine and betahistine, which are reported to be relatively potent H3 receptor antagonists, showed very low affinity. 5. Thioperamide (0.001-1 microM) alone enhanced the potassium-stimulated release of tritium in a concentration-dependent manner. Maximum effects were observed at 0.1-1 microM thioperamide, enhancing release by approximately 20%. 6. Results are discussed in terms of the regulatory role of H3 receptors on acetylcholine release and the possible existence of H3 receptor subtypes.

Full text

PDF
919

Selected References

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

  1. Arrang J. M., Garbarg M., Lancelot J. C., Lecomte J. M., Pollard H., Robba M., Schunack W., Schwartz J. C. Highly potent and selective ligands for histamine H3-receptors. Nature. 1987 May 14;327(6118):117–123. doi: 10.1038/327117a0. [DOI] [PubMed] [Google Scholar]
  2. Arrang J. M., Garbarg M., Quach T. T., Dam Trung TuongM, Yeramian E., Schwartz J. C. Actions of betahistine at histamine receptors in the brain. Eur J Pharmacol. 1985 Apr 23;111(1):73–84. doi: 10.1016/0014-2999(85)90115-3. [DOI] [PubMed] [Google Scholar]
  3. Arrang J. M., Garbarg M., Schwartz J. C. Auto-inhibition of brain histamine release mediated by a novel class (H3) of histamine receptor. Nature. 1983 Apr 28;302(5911):832–837. doi: 10.1038/302832a0. [DOI] [PubMed] [Google Scholar]
  4. Barnes J. M., Barnes N. M., Costall B., Horovitz Z. P., Naylor R. J. Angiotensin II inhibits the release of [3H]acetylcholine from rat entorhinal cortex in vitro. Brain Res. 1989 Jul 3;491(1):136–143. doi: 10.1016/0006-8993(89)90095-4. [DOI] [PubMed] [Google Scholar]
  5. Hew R. W., Hodgkinson C. R., Hill S. J. Characterization of histamine H3-receptors in guinea-pig ileum with H3-selective ligands. Br J Pharmacol. 1990 Nov;101(3):621–624. doi: 10.1111/j.1476-5381.1990.tb14130.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ichinose M., Barnes P. J. Histamine H3-receptors modulate nonadrenergic noncholinergic neural bronchoconstriction in guinea-pig in vivo. Eur J Pharmacol. 1989 Dec 12;174(1):49–55. doi: 10.1016/0014-2999(89)90872-8. [DOI] [PubMed] [Google Scholar]
  7. Kilpatrick G. J., Michel A. D. Characterisation of the binding of the histamine H3 receptor agonist [3H] (R)-alpha methyl histamine to homogenates of rat and guinea-pig cortex. Agents Actions Suppl. 1991;33:69–75. doi: 10.1007/978-3-0348-7309-3_4. [DOI] [PubMed] [Google Scholar]
  8. Poli E., Stark H., Bertaccini G. Histamine H3-receptor activation inhibits acetylcholine release from the guinea pig myenteric plexus. Agents Actions. 1991 May;33(1-2):167–169. doi: 10.1007/BF01993157. [DOI] [PubMed] [Google Scholar]
  9. Schlicker E., Betz R., Göthert M. Histamine H3 receptor-mediated inhibition of serotonin release in the rat brain cortex. Naunyn Schmiedebergs Arch Pharmacol. 1988 May;337(5):588–590. doi: 10.1007/BF00182737. [DOI] [PubMed] [Google Scholar]
  10. Schlicker E., Fink K., Hinterthaner M., Göthert M. Inhibition of noradrenaline release in the rat brain cortex via presynaptic H3 receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989 Dec;340(6):633–638. doi: 10.1007/BF00717738. [DOI] [PubMed] [Google Scholar]
  11. Taylor S. J., Kilpatrick G. J. Characterization of histamine-H3 receptors controlling non-adrenergic non-cholinergic contractions of the guinea-pig isolated ileum. Br J Pharmacol. 1992 Mar;105(3):667–674. doi: 10.1111/j.1476-5381.1992.tb09036.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Timmerman H. Histamine H3 ligands: just pharmacological tools or potential therapeutic agents? J Med Chem. 1990 Jan;33(1):4–11. doi: 10.1021/jm00163a001. [DOI] [PubMed] [Google Scholar]
  13. Trzeciakowski J. P. Inhibition of guinea pig ileum contractions mediated by a class of histamine receptor resembling the H3 subtype. J Pharmacol Exp Ther. 1987 Dec;243(3):874–880. [PubMed] [Google Scholar]

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

RESOURCES