PREJUNCTIONAL AND POSTJUNCTIONAL INHIBITORY EFFECTS OF FENSPIRIDE ON GUINEA-PIG BRONCHI

Citation
V. Girard et al., PREJUNCTIONAL AND POSTJUNCTIONAL INHIBITORY EFFECTS OF FENSPIRIDE ON GUINEA-PIG BRONCHI, The European respiratory journal, 10(5), 1997, pp. 1015-1020
Citations number
20
Categorie Soggetti
Respiratory System
ISSN journal
09031936
Volume
10
Issue
5
Year of publication
1997
Pages
1015 - 1020
Database
ISI
SICI code
0903-1936(1997)10:5<1015:PAPIEO>2.0.ZU;2-5
Abstract
Fenspiride is a drug with potential benefits in the treatment of obstr uctive airways disease. It has antibronchoconstriction and anti-inflam matory properties, The aim of this study was to investigate the effect of this drug on the contractions induced in the guinea-pig isolated m ain bronchus and perfused lung by electrical field stimulation (EFS) o r exogenously added agents. Bronchi were stimulated transmurally in th e presence of indomethacin 10(-6) M and propranolol 10(-6) M, and isom etric tension was measured. In the perfused lung model, calcitonin gen e-related peptide (CGRP) release was determined in the perfusate fract ions as a measure of neuropeptide production. Two successive contracti le responses were observed: a rapid cholinergic contraction, followed by a long-lasting contraction due to local release of neuropeptides fr om C-fibre endings. Fenspiride (10(-6) to 10(-4) M) inhibited the nona drenergic, noncholinergic (NANC) component of the contraction of the g uinea-pig isolated main bronchus induced by EFS, Fenspiride significan tly affected contractions induced by exogenously added substance P or [Nle(10)]-NKA(4-10) only at concentrations higher than 10(-3) M. In th e guinea-pig perfused lung, fenspiride inhibited low pH- but not capsa icin-evoked release of CGRP, At higher concentrations (10(-4) M to 3x1 0(-4) M) fenspiride exhibited a significant inhibitory effect both on the cholinergic component of contractile response induced by EFS in th e guinea-pig isolated main bronchus and on exogenously added acetylcho line. In conclusion, the result of this study suggests that fenspiride , in moderate concentrations, reduces the release of neuropeptides, in cluding tachykinins, from sensory nerve endings at a prejunctional lev el. At higher concentrations, postjunctional actions on bronchial smoo th muscle arp also present.