Different effects of salmeterol, formoterol and salbutamol on cholinergic responses in the ferret trachea
(1995) In British Journal of Pharmacology 114(7). p.1478-1482- Abstract
- 1 In the present study, the inhibitory effects of the selective beta 2-adrenoceptor agonists, salmeterol, formoterol and salbutamol, have been investigated on contractions of ferret trachea induced both by endogenous and exogenous acetylcholine. The aim of the study was to evaluate quantitative and/or qualitative differences in response which may indicate both pre-and post-junctional sites of action. The non-selective beta-antagonist, sotalol, was used to estimate beta-adrenoceptor involvement.
2 Isometric tension was measured in ferret isolated tracheal strips. The inhibitory effects of the drugs
were studied on tonic contractions induced by re-junctional activation with electrical field stimulation (EFS) (2 Hz, 700 mA)... (More) - 1 In the present study, the inhibitory effects of the selective beta 2-adrenoceptor agonists, salmeterol, formoterol and salbutamol, have been investigated on contractions of ferret trachea induced both by endogenous and exogenous acetylcholine. The aim of the study was to evaluate quantitative and/or qualitative differences in response which may indicate both pre-and post-junctional sites of action. The non-selective beta-antagonist, sotalol, was used to estimate beta-adrenoceptor involvement.
2 Isometric tension was measured in ferret isolated tracheal strips. The inhibitory effects of the drugs
were studied on tonic contractions induced by re-junctional activation with electrical field stimulation (EFS) (2 Hz, 700 mA) or post-junctional activation with exogenous acetylcholine (ACh) (0.5 ltM, about EC80), giving a similar degree of smooth muscle response.
3 Concentration-response experiments were performed with formoterol (0.3 nM-0.3 tLM) and salmeterol and salbutamol (1O nM- 1O ikM). The experiments ended with the addition of sotalol (10 M).
4 All three beta-agonists inhibited the contractions in a concentration-dependent manner. Salbutamol, formoterol and salmeterol inhibited the EFS-induced contractions by 66(8)%, 105(5)% and 103(8)% (mean(s.e.mean)) respectively. ACh-induced contractions were inhibited by 37(6)%, 72(11)% and 33(8)%. Theophylline (10 nM-3 mM) inhibited the contractions to the same degree.
5 beta-Adrenoceptor blockade by sotalol significantly antagonized the inhibitory effects of salbutamol and
formoterol on both EFS- and ACh-induced contractions. The effect of salmeterol on ACh-induced contraction was also significantly antagonized, whereas the inhibition of EFS-induced contraction was virtually unaffected.
6 In conclusion, salbutamol, salmeterol and formoterol produced greater inhibitory effects in preparations
contracted by EFS than in preparations contracted by exogenously-added ACh. In the case of formoterol and salbutamol, the effects on both levels are most probably due to beta-adrenoceptor stimulation, whereas for salmeterol the dominant pre-junctional effect is probably not mediated via beta-adrenoceptors. This non-beta-mediated effect could represent an additional relaxant mechanism for salmeterol. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1109408
- author
- Bergendal, A ; Linden, A ; Lotvall, J ; Skoogh, B E and Löfdahl, Claes-Göran LU
- publishing date
- 1995
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- salmeterol, formoterol, salbutamol, pre-junctional beta-adrenoceptors, beta-Agonists, cholinergic responses
- in
- British Journal of Pharmacology
- volume
- 114
- issue
- 7
- pages
- 1478 - 1482
- publisher
- Wiley
- external identifiers
-
- pmid:7606351
- scopus:0028944817
- ISSN
- 1476-5381
- language
- English
- LU publication?
- no
- id
- 4a97110e-c2b7-40ff-b766-c2af8149c7d8 (old id 1109408)
- alternative location
- http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1510282
- date added to LUP
- 2016-04-01 15:53:55
- date last changed
- 2021-01-03 07:57:44
@article{4a97110e-c2b7-40ff-b766-c2af8149c7d8,
abstract = {{1 In the present study, the inhibitory effects of the selective beta 2-adrenoceptor agonists, salmeterol, formoterol and salbutamol, have been investigated on contractions of ferret trachea induced both by endogenous and exogenous acetylcholine. The aim of the study was to evaluate quantitative and/or qualitative differences in response which may indicate both pre-and post-junctional sites of action. The non-selective beta-antagonist, sotalol, was used to estimate beta-adrenoceptor involvement.<br/><br>
2 Isometric tension was measured in ferret isolated tracheal strips. The inhibitory effects of the drugs<br/><br>
were studied on tonic contractions induced by re-junctional activation with electrical field stimulation (EFS) (2 Hz, 700 mA) or post-junctional activation with exogenous acetylcholine (ACh) (0.5 ltM, about EC80), giving a similar degree of smooth muscle response. <br/><br>
3 Concentration-response experiments were performed with formoterol (0.3 nM-0.3 tLM) and salmeterol and salbutamol (1O nM- 1O ikM). The experiments ended with the addition of sotalol (10 M).<br/><br>
4 All three beta-agonists inhibited the contractions in a concentration-dependent manner. Salbutamol, formoterol and salmeterol inhibited the EFS-induced contractions by 66(8)%, 105(5)% and 103(8)% (mean(s.e.mean)) respectively. ACh-induced contractions were inhibited by 37(6)%, 72(11)% and 33(8)%. Theophylline (10 nM-3 mM) inhibited the contractions to the same degree.<br/><br>
5 beta-Adrenoceptor blockade by sotalol significantly antagonized the inhibitory effects of salbutamol and<br/><br>
formoterol on both EFS- and ACh-induced contractions. The effect of salmeterol on ACh-induced contraction was also significantly antagonized, whereas the inhibition of EFS-induced contraction was virtually unaffected.<br/><br>
6 In conclusion, salbutamol, salmeterol and formoterol produced greater inhibitory effects in preparations<br/><br>
contracted by EFS than in preparations contracted by exogenously-added ACh. In the case of formoterol and salbutamol, the effects on both levels are most probably due to beta-adrenoceptor stimulation, whereas for salmeterol the dominant pre-junctional effect is probably not mediated via beta-adrenoceptors. This non-beta-mediated effect could represent an additional relaxant mechanism for salmeterol.}},
author = {{Bergendal, A and Linden, A and Lotvall, J and Skoogh, B E and Löfdahl, Claes-Göran}},
issn = {{1476-5381}},
keywords = {{salmeterol; formoterol; salbutamol; pre-junctional beta-adrenoceptors; beta-Agonists; cholinergic responses}},
language = {{eng}},
number = {{7}},
pages = {{1478--1482}},
publisher = {{Wiley}},
series = {{British Journal of Pharmacology}},
title = {{Different effects of salmeterol, formoterol and salbutamol on cholinergic responses in the ferret trachea}},
url = {{http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1510282}},
volume = {{114}},
year = {{1995}},
}