| pubmed-article:15381630 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15381630 | lifeskim:mentions | umls-concept:C0458827 | lld:lifeskim |
| pubmed-article:15381630 | lifeskim:mentions | umls-concept:C0389995 | lld:lifeskim |
| pubmed-article:15381630 | lifeskim:mentions | umls-concept:C0700624 | lld:lifeskim |
| pubmed-article:15381630 | lifeskim:mentions | umls-concept:C1325847 | lld:lifeskim |
| pubmed-article:15381630 | lifeskim:mentions | umls-concept:C1155937 | lld:lifeskim |
| pubmed-article:15381630 | lifeskim:mentions | umls-concept:C1880177 | lld:lifeskim |
| pubmed-article:15381630 | lifeskim:mentions | umls-concept:C2349975 | lld:lifeskim |
| pubmed-article:15381630 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:15381630 | pubmed:dateCreated | 2004-10-15 | lld:pubmed |
| pubmed-article:15381630 | pubmed:abstractText | 1. Repeated allergen challenge has been shown to increase the role of Rho-kinase in airway smooth muscle (ASM) contraction. We considered the possibility that active allergic sensitization by itself, that is, without subsequent allergen exposure, could be sufficient to enhance Rho-kinase-mediated ASM contraction. 2. Guinea pigs were actively IgE-sensitized to ovalbumin (OA), using Al(OH)(3) as adjuvant. Contractile responsiveness to G(q)-coupled receptor agonists (methacholine, histamine or PGF(2alpha)) was investigated in tracheal rings. No effect of sensitization was observed on basal- and methacholine-induced myogenic tone. In contrast, potency of histamine and PGF(2alpha) increased, that is, EC(50) decreased, after OA-sensitization by 2.6- and 4.7-fold, respectively, without effect on maximal contraction (E(max)). 3. Basal tone in preparations from both control and OA-sensitized animals was strongly decreased in the presence of the Rho-kinase inhibitor (+)-(R)-trans-4-(1-aminoethyl)-N-(4-pyridyl) cyclohexane carboxamide (Y-27632) (1 microm). In control preparations, the E(max) and potency of histamine were unaffected by Y-27632, but were decreased for PGF(2alpha) (by 38.2% and 2.0-fold, respectively). However, in preparations from OA-sensitized animals, Y-27632 induced a significant reduction in E(max) (33.5%) and potency (2.3-fold) of histamine and of PGF(2alpha) (48.3% and 6.6-fold, respectively), normalizing the OA-sensitization-induced increase in sensitivity toward these agonists. 4. We also investigated the contribution of Rho-kinase in vivo by measuring airway responsiveness toward inhaled histamine in permanently instrumented, unanaesthetized control and OA-sensitized guinea pigs. Treatment with Y-27632 by inhalation (5 mm, nebulizer concentration) decreased airway responsiveness toward histamine both in control and OA-sensitized animals. However, the histamine PC(100) ratio pre/post Y-27632 inhalation was significantly smaller in OA-sensitized animals as compared to control animals, indicating an enhanced contribution of Rho-kinase. 5. Expression of RhoA, an upstream activator of Rho-kinase, was significantly increased (2.6-fold) in lung homogenates of OA-sensitized guinea pigs compared to control animals, as determined by Western analysis. 6. In conclusion, the results show a receptor-dependent role of Rho-kinase in agonist-induced ASM contraction. The contribution of Rho-kinase to contractile airway responsiveness, both in vivo and ex vivo, is augmented after active allergic sensitization, as a consequence of increased expression of RhoA presumably. Inhibition of the RhoA/Rho-kinase pathway may be considered a useful pharmacotherapeutical target in allergy and asthma. | lld:pubmed |
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| pubmed-article:15381630 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15381630 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15381630 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:15381630 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15381630 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:15381630 | pubmed:issn | 0007-1188 | lld:pubmed |
| pubmed-article:15381630 | pubmed:author | pubmed-author:ZaagsmaJohanJ | lld:pubmed |
| pubmed-article:15381630 | pubmed:author | pubmed-author:BosI Sophie... | lld:pubmed |
| pubmed-article:15381630 | pubmed:author | pubmed-author:MeursHermanH | lld:pubmed |
| pubmed-article:15381630 | pubmed:author | pubmed-author:NelemansS... | lld:pubmed |
| pubmed-article:15381630 | pubmed:author | pubmed-author:GosensReinoud... | lld:pubmed |
| pubmed-article:15381630 | pubmed:author | pubmed-author:SchaafsmaDedm... | lld:pubmed |
| pubmed-article:15381630 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15381630 | pubmed:volume | 143 | lld:pubmed |
| pubmed-article:15381630 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15381630 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15381630 | pubmed:pagination | 477-84 | lld:pubmed |
| pubmed-article:15381630 | pubmed:dateRevised | 2009-11-18 | lld:pubmed |
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| pubmed-article:15381630 | pubmed:meshHeading | pubmed-meshheading:15381630... | lld:pubmed |
| pubmed-article:15381630 | pubmed:year | 2004 | lld:pubmed |
| pubmed-article:15381630 | pubmed:articleTitle | Allergic sensitization enhances the contribution of Rho-kinase to airway smooth muscle contraction. | lld:pubmed |
| pubmed-article:15381630 | pubmed:affiliation | Department of Molecular Pharmacology, University of Groningen, A. Deusinglaan 1, 9713 AV Groningen, The Netherlands. | lld:pubmed |
| pubmed-article:15381630 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:15381630 | pubmed:publicationType | Comparative Study | lld:pubmed |
| pubmed-article:15381630 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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