Histamine H3-receptors inhibit cholinergic neurotransmission in guinea-pig airways

Br J Pharmacol. 1989 May;97(1):13-5. doi: 10.1111/j.1476-5381.1989.tb11917.x.


The histamine H3-agonist (R)-alpha-methylhistamine (alpha-MeHA) caused a dose-dependent inhibition of vagally-mediated contraction of a guinea-pig tracheal tube preparation but did not alter tracheal contraction induced by exogenously-applied acetylcholine. Blockade of H1- and H2-histamine receptors, and alpha- and beta-adrenoceptors failed to prevent the inhibitory effect of alpha-MeHA, whereas the specific H3-antagonist thioperamide prevented the effect of alpha-MeHA on tracheal contraction. In the presence of H1- and H2-receptor antagonists, histamine also inhibited vagally-mediated tracheal contraction. The inhibitory effect of alpha-MeHA was greater with preganglionic (vagus nerve) stimulation than with postganglionic stimulation by electrical field stimulation, suggesting that H3-receptors are localized both to cholinergic ganglia and to post-ganglionic nerve-endings. Our results suggest that H3-receptors exist on the vagus nerve which modulate cholinergic neurotransmission in the airways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Astemizole
  • Benzimidazoles / pharmacology
  • Cimetidine / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Methylhistamines / pharmacology
  • Parasympathetic Nervous System / drug effects
  • Parasympathetic Nervous System / physiology*
  • Receptors, Histamine / drug effects
  • Receptors, Histamine / physiology*
  • Respiratory System / innervation*
  • Synaptic Transmission*
  • Trachea / innervation


  • Benzimidazoles
  • Methylhistamines
  • Receptors, Histamine
  • Astemizole
  • Cimetidine
  • N-methylhistamine