JPET xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Knott, P. G.
Right arrow Articles by Goldie, R. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Knott, P. G.
Right arrow Articles by Goldie, R. G.

Influence of endothelin-1 on cholinergic nerve-mediated contractions and acetylcholine release in rat isolated tracheal smooth muscle

PG Knott, LB Fernandes, PJ Henry and RG Goldie

Department of Pharmacology, University of Western Australia, Nedlands, Australia.

The aim of this study was to assess the influence of endothelin-1 (ET- 1) on cholinergic nerve-mediated contractions in rat isolated tracheal smooth muscle by use of electrical-field stimulation (EFS) and [3H]choline efflux studies. EFS (80 V, 0.5 ms, 0.1-30 Hz for 10 s) evoked transient, frequency-dependent contractions of isolated tracheal preparations. Contractions were abolished in the presence of atropine or tetrodotoxin, which suggests they were mediated by acetylcholine (ACh) release from cholinergic nerves. The ETB receptor-selective agonist sarafotoxin S6c (1 nM) augmented EFS (0.6-1 Hz)-induced contractions by 179%. These effects were significantly attenuated in the presence of the ETB receptor-selective antagonist N-cis-2,6- dimethylpiperidinocarbonyl-L-gamma-methyl-leucyl-D-1- methoxycarbonyltryptophanyl-D-norleucine (BQ-788; 1 microM). ET-1 (1 nM) also markedly potentiated EFS-induced contractions (153%). This was apparently not a postjunctional effect, because ET-1 did not alter contractile responses to exogenously applied ACh. Cyclo[D-Trp-D-Asp-L- Pro-D-Val-L-Leu] (BQ-123;3 microM) and BQ-788 when used alone, failed to inhibit ET-1-induced potentiation of EFS-evoked contractions. However, in their combined presence, BQ-123 and BQ-788 significantly attenuated ET-1-induced potentiation of EFS responses. EFS (100 V, 0.5 ms, 3 Hz for 2 min) applied to tracheal preparations preloaded with [3H]choline, caused airway smooth muscle contraction and an efflux of radioactivity. Both sarafotoxin S6c (10 nM) and ET-1 (10 nM) significantly enhanced the EFS-induced 3H-efflux and the latter was abolished only in the combined presence of BQ-123 and BQ-788. These data indicated that ET-1 enhances cholinergic nerve-mediated contractions in rat isolated trachea via activation of prejunctional ETA and ETB receptors that were linked to increased ACh release from cholinergic nerves.

Volume 279, Issue 3, pp. 1142-1147, 12/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics




This article has been cited by other articles:


Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
P. J. Henry, T. S. Mann, A. C. D'Aprile, G. J. Self, and R. G. Goldie
An endothelin receptor antagonist, SB-217242, inhibits airway hyperresponsiveness in allergic mice
Am J Physiol Lung Cell Mol Physiol, November 1, 2002; 283(5): L1072 - L1078.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1996 by the American Society for Pharmacology and Experimental Therapeutics.