Linked Life Data

17237191

Source:http://linkedlifedata.com/resource/pubmed/id/17237191

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-4-13
pubmed:abstractText
The aim of the present study was to provide a mechanistic insight into how 14,15-epoxyeicosatrienoic acid (EET) relaxes organ-cultured human bronchi. Tension measurements, performed on either fresh or 3-d-cultured bronchi, revealed that the contractile responses to 1 microM methacholine and 10 microM arachidonic acid were largely relaxed by the eicosanoid regioisomer in a concentration-dependent manner (0.01-10 microM). Pretreatments with 14,15-epoxyeicosa-5(Z)-enoic acid, a specific 14,15-EET antagonist, prevented the relaxing effect, whereas iberitoxin pretreatments (10 nM) partially abolished EET-induced relaxations. In contrast, pretreatments with 1 microM indomethacin amplified relaxations in explants and membrane hyperpolarizations triggered by 14,15-EET on airway smooth muscle cells. The relaxing responses induced by 14,15-EET were likely related to reduced Ca2+ sensitivity of the myofilaments, because free Ca2+ concentration-response curves performed on beta-escin-permeabilized cultured explants were shifted toward higher [Ca2+] (lower pCa2+ values). 14,15-EET also abolished the tonic responses induced by phorbol-ester-dybutyrate (PDBu) (a protein kinase C [PKC]-sensitizing agent), on both fresh (intact) and beta-escin-permeabilized explants. Western blot analyses, using two specific primary antibodies against CPI-17 and its PKC-dependent phosphorylated isoform (p-CPI-17), confirmed that the eicosanoid interferes with this intracellular process. These data indicate that 14,15-EET hyperpolarizes airway smooth muscle cells and relaxes precontracted human bronchi while reducing Ca2+ sensitivity of fresh and cultured explants. The intracellular effects are related to a PKC-dependent process involving a lower phosphorylation level of CPI-17.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/14,15-episulfide eicosatrienoic acid, http://linkedlifedata.com/resource/pubmed/chemical/14,15-epoxy-5,8,11-eicosatrienoic..., http://linkedlifedata.com/resource/pubmed/chemical/8,11,14-Eicosatrienoic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Amides, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/N-methylsulfonyl-6-(2-propargyloxyph..., http://linkedlifedata.com/resource/pubmed/chemical/PPP1R14A protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Phorbol Esters, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases, http://linkedlifedata.com/resource/pubmed/chemical/Potassium, http://linkedlifedata.com/resource/pubmed/chemical/Potassium Channels...
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1044-1549
pubmed:author
pubmed:issnType
Print
pubmed:volume
36
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
633-41
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Epoxyeicosatrienoic acid relaxing effects involve Ca2+-activated K+ channel activation and CPI-17 dephosphorylation in human bronchi.
pubmed:affiliation
Le Bilarium, Department of Physiology and Biophysics, Service of Thoracic Surgery, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001 12th Avenue North, Sherbrooke, PQ, J1H 5N4 Canada.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't