Source:http://linkedlifedata.com/resource/pubmed/id/11602678
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
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| pubmed:dateCreated |
2001-10-16
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| pubmed:abstractText |
OPC-28326 has been reported to selectively increase femoral blood flow in open-chest dogs and autoperfused canine femoral artery preparations. Preliminary data indicated that OPC-28326 has a high affinity at the alpha2-adrenoceptor. In the present study, we tested OPC-28326 in isoflurane anesthetized rats at a dose of 3 mg/kg of body weight, given intraduodenally. OPC-28326 significantly increased femoral blood flow, by 44.7 +/- 13.8%, 45 min after drug administration, whereas carotid blood flow increased by only 3.6 +/- 5.5% (n = 6). Chinese hamster ovary cell lines overexpressing rat alpha2D-, alpha2B-, or alpha2C-adrenoceptor were established. These cells also coexpress luciferase, driven by cAMP elevation. In radioligand binding assays using cell membrane preparations, OPC-28326 dose dependently competed with [3H]RX821002 binding, with calculated K(i) values of 3840 +/- 887, 633 +/- 46, and 13.7 +/- 1.9 nM on alpha2D-, alpha2B-, and alpha2C-adrenoceptor, respectively. A similar affinity and rank order of potency were also found for OPC-28326 on the alpha2-subtypes using epinephrine as agonist in luciferase assays. No agonistic effect of OPC-28326 was detected on any of the alpha2-adrenoceptors. Finally, in situ hybridization performed on skeletal muscle tissue sections collected from rat hind limb (musculus gastrocnemius) demonstrated a high level expression of alpha2C in the vascular tissues. Thus, the abundance of alpha2C in the skeletal muscle may account for the selective effect of OPC-28326 in increasing femoral blood flow.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-2 Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic alpha-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Alprostadil,
http://linkedlifedata.com/resource/pubmed/chemical/Aniline Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/OPC 28326,
http://linkedlifedata.com/resource/pubmed/chemical/Piperidines,
http://linkedlifedata.com/resource/pubmed/chemical/Vasodilator Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Yohimbine
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0022-3565
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
299
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
652-8
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:11602678-Adrenergic alpha-2 Receptor Antagonists,
pubmed-meshheading:11602678-Adrenergic alpha-Antagonists,
pubmed-meshheading:11602678-Alprostadil,
pubmed-meshheading:11602678-Aniline Compounds,
pubmed-meshheading:11602678-Animals,
pubmed-meshheading:11602678-CHO Cells,
pubmed-meshheading:11602678-Cloning, Molecular,
pubmed-meshheading:11602678-Cricetinae,
pubmed-meshheading:11602678-Femoral Vein,
pubmed-meshheading:11602678-Hindlimb,
pubmed-meshheading:11602678-In Situ Hybridization,
pubmed-meshheading:11602678-Luciferases,
pubmed-meshheading:11602678-Male,
pubmed-meshheading:11602678-Piperidines,
pubmed-meshheading:11602678-Radioligand Assay,
pubmed-meshheading:11602678-Rats,
pubmed-meshheading:11602678-Rats, Sprague-Dawley,
pubmed-meshheading:11602678-Regional Blood Flow,
pubmed-meshheading:11602678-Vasodilator Agents,
pubmed-meshheading:11602678-Yohimbine
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| pubmed:year |
2001
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| pubmed:articleTitle |
OPC-28326, a selective femoral vasodilator, is an alpha2C-adrenoceptor-selective antagonist.
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| pubmed:affiliation |
Vascular Biology and Circulation, Maryland Research Laboratories, Otsuka Maryland Research Institute, Rockville, MD 20850, USA. bings@otsuka.com
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| pubmed:publicationType |
Journal Article,
In Vitro
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