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

The histamine H₃-agonist (R)-α-methylhistamine (α-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 α- and β-adrenoceptors failed to prevent the inhibitory effect of α-MeHA, whereas the specific H₃-antagonist thioperamide prevented the effect of α-MeHA on tracheal contraction. In the presence of H₁- and H₂-receptor antagonists, histamine also inhibited vagally-mediated tracheal contraction. The inhibitory effect of α-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 thatl H₃-receptors exist on the vagus nerve which modulate cholinergic neurotransmission in the airways.