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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1998-6-8
pubmed:abstractText
The role of endogenous 5-lipoxygenase products in modulating tachykinergic neurotransmission in guinea pig isolated trachea was investigated. Tachykinin-containing afferent nerve fibers were stimulated with either electrical field stimulation or antidromic stimulation of the right vagus nerve. This resulted in contractions of the isolated caudal trachea and bronchus that could be blocked with either tetrodotoxin or a combination of neurokinin-1 and neurokinin-2 receptor antagonists. The 5-lipoxygenase inhibitor ZD 2138 (1 microM) significantly inhibited these neurally mediated tachykinergic contractions, by approximately 50%, yet had no effect on the contractions evoked by stimulating tachykinergic fibers in an action potential-independent fashion with capsaicin or by exogenously applied neurokinin A. The effect of ZD 2138 on action potential-driven tachykinergic contractions was mimicked by pobilukast, pranlukast, montelukast and zafirlukast, four structurally unrelated antagonists of the cysteinyl leukotriene 1 receptor subtype. Pobilukast had no effect on the tachykinergic contraction in tissues pretreated with ZD 2138. Likewise, ZD 2138 had no effect on the tachykinergic contractions in tissues pretreated with pobilukast. Intracellular electrophysiological recording of the membrane properties of jugular ganglion neurons, the source of tachykinins in the guinea pig trachea/bronchus, demonstrated that leukotriene D4 caused a membrane depolarization of vagal afferent C-fiber neurons and an increase in input impedance, both of which were abolished by zafirlukast. Taken together, these data indicate that in the resting guinea pig isolated trachea/bronchus, endogenous 5-lipoxygenase activity leads to the production of cysteinyl leukotrienes that amplify action potential-dependent release of tachykinins from airway afferent nerve fibers.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
602-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Inhibition of 5-lipoxygenase diminishes neurally evoked tachykinergic contraction of guinea pig isolated airway.
pubmed:affiliation
Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.