Linked Life Data

9458798

Source:http://linkedlifedata.com/resource/pubmed/id/9458798

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1 Pt 1
pubmed:dateCreated
1998-2-19
pubmed:abstractText
The beta 2-agonists currently used as bronchodilators are racemic mixtures of R- and S-enantiomers. In the present study, we examined the effects of enantiomers of the beta 2-agonists albuterol and formoterol on acetylcholine (ACh) release from equine trachealis parasympathetic nerves. ACh release was evoked by electrical field stimulation (20 V, 0.5 ms, 0.5 Hz) and measured by high-performance liquid chromatography coupled with electrochemical detection. We also tested the effects of enantiomers of albuterol and formoterol on equine tracheal smooth muscle (TSM) contraction in response to exogenous ACh. R- and RS-albuterol (10(-8) to 10(-5) M) and RR- and RR/SS-formoterol (10(-8) to 10(-5) M) augmented ACh release in a concentration-dependent manner. Beginning at 10(-6) M, SS-formoterol significantly increased ACh release, and at 10(-5) M, release increased by 71.9 +/- 8.7% over baseline. This effect was only observed, however, when the prejunctional muscarinic autoinhibitory effect of ACh was prevented with atropine. Both the RR- and SS-formoterol-induced increases in ACh release were abolished by the beta 2-antagonist ICI-118551 (3 x 10(-7) M). The effect of S-albuterol on ACh release was variable, and the mean increase induced by 10(-5) M was 30.8 +/- 16.1% in the presence of atropine. In the muscle tension study, R- and RS-albuterol and RR- and RR/SS-formoterol (10(-8) to 10(-5) M) but not the S-enantiomers inhibited TSM contraction. Even though R-enantiomers augment ACh release, they potently inhibit TSM contraction. Because racemic beta 2-agonists are bronchodilators on acute administration, the postjunctional spasmolytic effects of R-enantiomers predominate over the spasmogenic effect evoked via increased ACh release. The S-enantiomers, in contrast, do not inhibit TSM contraction and therefore would not contribute to the observed bronchodilation of the racemate. The S-enantiomers do prejunctionally facilitate ACh release when prejunctional muscarinic autoreceptors are dysfunctional, suggesting a potentially deleterious effect.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0002-9513
pubmed:author
pubmed:issnType
Print
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
L32-8
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Effects of enantiomers of beta 2-agonists on ACh release and smooth muscle contraction in the trachea.
pubmed:affiliation
Department of Large Animal Clinical Sciences, Michigan State University, East Lansing 48824-1314, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't