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 that H3‐receptors exist on the vagus nerve which modulate cholinergic neurotransmission in the airways.