Linked Life Data

16601951

Source:http://linkedlifedata.com/resource/pubmed/id/16601951

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-5-16
pubmed:abstractText
The present study investigates the action of zinterol at beta(3)-adrenoceptors. We used mouse primary brown adipocytes and Chinese hamster ovary (CHO-K1) cells expressing the mouse or human beta(3)-adrenoceptor. Zinterol was a full agonist at increasing cyclic AMP levels in primary brown adipocytes (which express beta(1)- and beta(3)-adrenoceptors but not beta(2)-adrenoceptors), and this effect was almost totally abolished in adipocytes derived from beta(3)-adrenoceptor knock-out (KO) mice. Zinterol was also a full agonist at increasing another biological end-point, glucose uptake in brown adipocytes. This effect was reduced in adipocytes derived from beta(3)-adrenoceptor KO mice, with the remaining response sensitive to beta(1)-adrenoceptor antagonism. To determine whether the effect of zinterol on beta(3)-adrenoceptors in primary brown adipocytes can be replicated in a recombinant system, we used CHO-K1 cells expressing the mouse or human beta(3)-adrenoceptor. Zinterol was a full agonist at mouse and human receptors with respect to increasing cyclic AMP levels, with pEC(50) values similar to that of the selective beta(3)-adrenoceptor agonist (R, R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]-amino]-propyl]1,3-benzodioxole-2,2-dicarboxylate (CL316243) at the mouse receptor. At the human receptor, zinterol was more potent at increasing cyclic AMP levels than CL316243. In cytosensor microphysiometer studies, zinterol was a full agonist for increases in extracellular acidification rates at the mouse and human beta(3)-adrenoceptor. Therefore, we have shown that zinterol is a potent, high-efficacy beta(3)-adrenoceptor agonist at the endogenous mouse beta(3)-adrenoceptor in primary brown adipocytes and at the cloned mouse and human beta(3)-adrenoceptor expressed in CHO-K1 cells. Zinterol is therefore one of few beta-adrenoceptor agonists with high potency and efficacy at the human beta(3)-adrenoceptor.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0028-1298
pubmed:author
pubmed:issnType
Print
pubmed:volume
373
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
158-68
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:16601951-Adipocytes, pubmed-meshheading:16601951-Adipose Tissue, Brown, pubmed-meshheading:16601951-Adrenergic beta-3 Receptor Agonists, pubmed-meshheading:16601951-Adrenergic beta-Agonists, pubmed-meshheading:16601951-Albuterol, pubmed-meshheading:16601951-Animals, pubmed-meshheading:16601951-CHO Cells, pubmed-meshheading:16601951-Cloning, Molecular, pubmed-meshheading:16601951-Cricetinae, pubmed-meshheading:16601951-Cricetulus, pubmed-meshheading:16601951-Cyclic AMP, pubmed-meshheading:16601951-Ethanolamines, pubmed-meshheading:16601951-Extracellular Space, pubmed-meshheading:16601951-Glucose, pubmed-meshheading:16601951-Humans, pubmed-meshheading:16601951-Isoproterenol, pubmed-meshheading:16601951-Mice, pubmed-meshheading:16601951-Mice, Knockout, pubmed-meshheading:16601951-Receptors, Adrenergic, beta-3
pubmed:year
2006
pubmed:articleTitle
Agonist effects of zinterol at the mouse and human beta(3)-adrenoceptor.
pubmed:affiliation
Department of Physiology, The Wenner-Gren Institute, Arrhenius Laboratory F3, Stockholm University, 10691 Stockholm, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't