liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
An indomethacin-sensitive contraction induced by β-antagonists in guinea pig airways
Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Medicine and Care, Pharmacology. Linköping University, Faculty of Health Sciences.
2004 (English)In: Canadian Journal of Physiology and Pharmacology, ISSN 0008-4212, E-ISSN 1205-7541, Vol. 82, no 6, 393-401 p.Article in journal (Refereed) Published
Abstract [en]

β-adrenergic receptor (β-AR) antagonists have been associated with increased airway reactivity in asthmatics and potentiation of contractile stimuli in animal models. In the present study, using an in vitro model of tracheal preparations from guinea pigs, we show that the β-AR antagonists propranolol and pindolol induce a smooth muscle contraction. A prerequisite for this contraction is that the airway preparations have been pre-treated with an β-AR agonist. Our data show that the contractile effect of β-AR antagonists is not a simple consequence of reversing the agonist-induced relaxation. Furthermore, the effect seems to be mediated through interaction with β2-ARs since the response is stereo-selective, and the selective β1-AR receptor antagonist atenolol did not induce any contractile response. SQ 29,546, a thromboxane A2 antagonist; MK 886, a lipoxygenase inhibitor; and indomethacin, a cyclooxygenase inhibitor significantly inhibited the contractions of the tracheal preparations induced with propranolol or pindolol. We put forward the hypothesis that the contractile effect of the β-AR antagonist is a consequence of their inverse agonist activity, which is only evident when the receptor population have a higher basal activity. Our results indicate a novel additional explanation for the known side effect, bronchoconstriction, of β-AR antagonist.Key words: beta antagonist, guinea pig trachea, propranolol, formoterol, pindolol, indomethacin.

Place, publisher, year, edition, pages
2004. Vol. 82, no 6, 393-401 p.
Keyword [en]
beta antagonist, guinea pig trachea, propranolol, formoterol, pindolol, indomethacin
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-23707DOI: 10.1139/y04-039Local ID: 3208OAI: oai:DiVA.org:liu-23707DiVA: diva2:244022
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2017-12-13Bibliographically approved
In thesis
1. Bronchial hyperresponsiveness of ß-adrenoceptor agonists and antagonists in guinea pig airways
Open this publication in new window or tab >>Bronchial hyperresponsiveness of ß-adrenoceptor agonists and antagonists in guinea pig airways
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Asthma is one of the most common diseases in the industrialised countries. The underlying mechanisms are complex and still not fully understood although inflammation of the airways plays an important role. There are to day several types of drugs used in the treatment of asthma such as anti-inflammatory drugs, specific antagonists for inflammatory mediators and bronchodilators. Beta-agonists are the main choice for relaxing airway constriction, however unwanted effects of beta-agonists on patients with asthma has been reported. The betaantagonists that are used for treatment of hypertension and various other conditions also is shown to be deleterious in asthmatics. In the present study we have used guinea pig airways to examine the proposed deleterious effects of beta-agonists and antagonists. We have shown that the (S)-enantiomeric forms of salbutamol and formoterol are able to potentiate cholinergic stimuli and we have shown that the potentiation was indomethacin sensitive in airway preparations of sensitised guinea pigs. We also showed and confirmed that the (R)-enantiomeric forms of salbutamol and formoterol were more potent in relaxing airway smooth muscle contracted with different stimuli compared to the (S)-enantiomers. The betaantagonists propranolol and pindolol were shown to be able to contract tracheal preparations if they had been pre-treated with a beta-agonist and the contraction was not simply a blockade of the beta-adrenoceptor induced relaxation. Propranolol contraction was stereo-selective and (S)-propranolol was more effective in inducing contraction than (R)-propranolol. Moreover, atenolol a betacselective antagonist induced significantly smaller contractions compared to general beta-antagonists. This indicates that the beta2-adrenocepor probably is involved in the beta-antagonist induced contraction. The cyclooxygenase inhibitor indomethacin, the 5-lipoxygenase inhibitor MK886 and a thromboxane A2 antagonist as well as capsaicin reduced the beta-antagonist induced contraction. This indicates that several arachidonic acid products as well as neuropeptides may be involved in the beta-antagonistinduced contraction.

The worsening of asthma by beta-antagonists is well known and the risks associated with beta-agonists are discussed, but the mechanisms behind these effects need further clarification. In this thesis some of the possible mechanism have been discussed, further studies are needed in order to get more safe and effective asthma treatment regime.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2003. 66 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 780
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-27499 (URN)12153 (Local ID)91-7373-541-8 (ISBN)12153 (Archive number)12153 (OAI)
Public defence
2003-04-10, Viktoriasalen, Hälsouniversitet, Linköping, 13:00 (Swedish)
Opponent
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-10-15Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Authority records BETA

Johansson, FredrikAndersson, RolfLindström, EvaSvensson, Samuel

Search in DiVA

By author/editor
Johansson, FredrikAndersson, RolfLindström, EvaSvensson, Samuel
By organisation
PharmacologyFaculty of Health Sciences
In the same journal
Canadian Journal of Physiology and Pharmacology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 100 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf