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Different effects of salmeterol, formoterol and salbutamol on cholinergic responses in the ferret trachea

Bergendal, A; Linden, A; Lotvall, J; Skoogh, B E and Löfdahl, Claes-Göran LU (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)
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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
The British Pharmacological Society
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
2008-07-28 14:17:21
date last changed
2017-01-01 06:49:51
@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},
  keyword      = {salmeterol,formoterol,salbutamol,pre-junctional beta-adrenoceptors,beta-Agonists,cholinergic responses},
  language     = {eng},
  number       = {7},
  pages        = {1478--1482},
  publisher    = {The British Pharmacological Society},
  series       = {British Journal of Pharmacology},
  title        = {Different effects of salmeterol, formoterol and salbutamol on cholinergic responses in the ferret trachea},
  volume       = {114},
  year         = {1995},
}