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

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 beta-adrenoceptor-, acetylcholine, H1- and H2-receptor-mediated responses, respectively. Vagal stimulation evoked a NANC bronchoconstrictor response. The selective H3-agonist, alpha-methylhistamine (alpha-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 less than 0.02). Histamine itself also had a significant inhibitory effect on NANC responses with H1- and H2-blockade. The alpha-adrenoceptor antagonist phentolamine had no effect on the inhibitory response produced by alpha-MeHA, but the H3-receptor antagonist thioperamide blocked the inhibitory effect of alpha-MeHA. alpha-MeHA had no inhibitory effect on bronchoconstriction induced by exogenous substance P (5-25 micrograms/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.

journal_name

Eur J Pharmacol

authors

Ichinose M,Barnes PJ

doi

10.1016/0014-2999(89)90872-8

subject

Has Abstract

pub_date

1989-12-12 00:00:00

pages

49-55

issue

1

eissn

0014-2999

issn

1879-0712

pii

0014-2999(89)90872-8

journal_volume

174

pub_type

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