Histamine H3-receptors modulate nonadrenergic noncholinergic neural bronchoconstriction in guinea-pig in vivo

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Abstract

We have investigated whether the histamine H3-receptors influence nonadrenergic noncholinergic (NANC) bronchoconstriction in guinea-pig in vivo. Atropine, propranolol, mepyramine and cimetidine were administered to block the effects of β-adrenoceptor-, acetylcholine, H1- and H2-receptor-mediated responses, respectively. Vagal stimulation evoked a NANC bronchoconstrictor response. The selective H3-agonist, α-methylhistamine (α-MeHA, 1–10 mg/kg i.v.) did not alter basal respiratory insufflation pressure, but reduced the NANC bronchoconstrictor response to vagal stimulation in dose-dependent manner (with a maximal inhibition of 46.0 ± 10.3%; mean ± S.E. at 10 mg/kg) (P < 0.02). Histamine itself also had a significant inhibitory effect on NANC responses with H1- and H2-blockade. The α-adrenoceptor antagonist phentolamine had no effect on the inhibitory response produced by α-MeHA, but the H3-receptor antagonist thioperamide blocked the inhibitory effect of α-MeHA. α-MeHA had no inhibitory effect on bronchoconstriction induced by exogenous substance P (5–25 μg/kg i.v.). We conclude that H3-receptors inhibit the release of transmitter from NANC nerves and that H3-receptors might play a role in regulation of neurogenic inflammatory responses in the airways.

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