Bronchodilatation of guinea‐pig perfused bronchioles induced by the H₃‐receptor for histamine: role of epithelium

Abstract

I The influence of epithelium on the effects of H3-histamine receptor agonist (R)a-methylhistamine [(R)a-MeHist] on airways was investigated on the guinea-pig perfused bronchioles. 2 In preparations under resting tone, removal of the bronchiolar epithelium or treatment with the cyclo-oxygenase inhibitor indomethacin (10' M) increased the constriction induced by histamine and acetylcholine in a concentration-dependent manner without an alteration of the K+-induced contraction. 3 In this preparation (R)a-MeHist induced a concentration-dependent bronchodilatation which was antagonized in a competitive manner by thioperamide (an H3-antagonist) with a pA2 value of 8.6. 4 This bronchodilatation was reversed to a low concentration-dependent constriction after either removal of the epithelium or treatment with indomethacin (10-' M) but was unaffected by both 10-5 M tranylcypromine (an inhibitor of PGI2 synthesis) and 5 x 10-5M NG-nitro-L-arginine methyl ester (an inhibitor of NO synthesis).5 It is suggested that, in guinea-pig perfused bronchioles (R)x-MeHist induces an epithelium-dependent relaxation via the release of metabolite(s) of arachidonic acid.

The Histamine H3Receptor: Structure, Pharmacology, and Function

“…Stimulation of Phospholipase A 2 . The activation of phospholipase A 2 by the H 3 R induces the release of arachidonic acid, docosahexaenoic acid, and lysophospholipids, inducing functional consequences such as the relaxation of guinea pig bronchioles by enhanced release of the endothelium-derived relaxing factor, a metabolite of arachidonic acid (Burgaud and Oudart, 1993).…”

Effect of histamine on lung contractile elements in growing cattle

“…However, in our investigation, a substantial histamine-induced contraction was observed in the trachealis muscle in young adult cattle, but that observed in the bronchi was only slight, even at very high concentrations (10 -3 M). 20,21 Finally, a third explanation may be that, in cattle, the density of the H1 receptors in bronchial smooth muscles declines from the central to the peripheral airways. 19 The slight contraction of bronchi could be explained by masking of the H1-dependent bronchoconstrictor effect by a powerful H2-dependent bronchodilator effect.…”

N G-Nitro-l-arginine methyl ester inhibits the effect of an H3-histaminergic receptor agonist on NANC contraction in guinea-pig perfused bronchioles

“…Responses to electrical field stimulation were obtained at 10-min intervals in the presence of atropine (2 x lo-* M) and phentolamine (2 x When we tested the effect of (R)-a-MeHA on electrical field stimulation-induced contraction, tissues were incubated for 10 min with increasing concentrations of H3-agonist (2 x 2 x lo-' M). Parallel experiments were carried out in the presence of L-NAME (50 p~) (Burgaud & Oudart 1993b), L-arginine (50 p~) , a mixture of L-NAME and L-arginine, D-NAME (50 PM) or D-arginine (50 p~) added to the perfusate 30 min before beginning the series of agonist concentrations.…”

“…Responses to electrical field stimulation were obtained at 10-min intervals in the presence of atropine (2 x lo-* M) and phentolamine (2 x When we tested the effect of (R)-a-MeHA on electrical field stimulation-induced contraction, tissues were incubated for 10 min with increasing concentrations of H3-agonist (2 x 2 x lo-' M). Parallel experiments were carried out in the presence of L-NAME (50 p~) (Burgaud & Oudart 1993b), L-arginine (50 p~) , a mixture of L-NAME and L-arginine, D-NAME (50 PM) or D-arginine (50 p~) added to the perfusate 30 min before beginning the series of agonist concentrations.Cumulative concentration-response curves for substance P (2 x 10-IO-2 x lo-' M) or neurokinin A (10-lo-5 x lo-' M) were recorded by adding the substances to the tissue bath. To determine whether L-arginine modified contraction induced by substance P or neurokinin A, we introduced the NO-precursor (50 p~) in the organ bath 30 min before the series of agonist concentrations.…”