Bronchodilator Action of an Agonist for Histamine H3-receptors in Guinea Pig Perfused Bronchioles and Lung Parenchymal Strips

Overview

Journal Lung

Specialty Pulmonary Medicine

Date 1992 Jan 1

PMID 1323735

Citations 4

Authors

J L Burgaud

J Javellaud

N Oudart

Affiliations

Soon will be listed here.

Abstract

Isolated guinea pig perfused bronchioles and lung parenchymal strips were examined as an in vitro model for assessment of the direct effect of pharmacologic agents on the airway smooth muscle. The experiments were performed with a perfusion technique in bronchioles, the input pressure being measured as an index of the state of dilation, while changes in tension of the lung parenchymal strips were measured with an isometric force transducer. In both preparations, histamine and acetylcholine elicited dose-related contractile responses whereas fenoterol induced a concentration-dependent relaxation. After the 3 agonists' activities were compared in these 2 preparations, we tested the intrinsic effects of a specific H3 agonist, (R) alpha-methylhistamine ([R] alpha-MeHA). Statistical analysis was by Student's t test on the Emax (expressed as a percentage of 10(-4) M papaverine relaxation), EC50, and slopes of regression lines calculated from the concentration-response curves plotted for (R) alpha-MeHA alone or in presence of antagonists. Our results showed that (R) alpha-MeHA induced a concentration-dependent relaxation of perfused bronchioles and lung parenchymal strips competitively inhibited by 10(-7) M thioperamide (H3-antagonist), whereas 10(-5) M cimetidine (H2-antagonist) failed to prevent this effect. These results suggest the presence of H3-histaminergic dilatory receptors in the guinea pig airway.

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