Histamine H3-receptors inhibit cholinergic neurotransmission in guinea-pig airways.
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.
Ichinose
M
M
Department of Thoracic Medicine, National Heart and Lung Institute, London.
Stretton
C D
CD
Schwartz
J C
JC
Barnes
P J
PJ
D000818:Animals; D016589:Astemizole; D001562:Benzimidazoles / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D011968:Receptors, Histamine / Q000187:drug effects / Q000502:physiology*; D012137:Respiratory System / Q000294:innervation*; D009435:Synaptic Transmission; D014132:Trachea / Q000294:innervation
D001562:Benzimidazoles; D008761:Methylhistamines; D011968:Receptors, Histamine; D016589:Astemizole; D002927:Cimetidine; C048140:N-methylhistamine