|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
3
|
|
pubmed:dateCreated |
2002-9-18
|
|
pubmed:abstractText |
1 It has recently been reported that CGP 12177 can act as an agonist at a novel secondary site within the human beta(1)-adrenoceptor. The aim of this study was to undertake a detailed pharmacological study of the effects of CGP 12177 on the human beta(2)-adrenoceptor. 2 CGP 12177 acted as a potent partial agonist of (3)H-cyclic AMP accumulation (log EC(50)-8.90+/-0.06) and CRE-mediated reporter gene transcription (log EC(50)-9.66+/-0.04) in CHO-K1 cells expressing the human beta(2)-adrenoceptor. These CGP-induced responses were antagonized by the beta(2)-selective antagonist ICI 118551 (apparent log K(D) values of -8.84+/-0.15 and -9.51+/-0.02 for the cyclic AMP and reporter gene responses respectively). 3 CGP 12177 was also able to antagonize both cyclic AMP and reporter gene responses to more efficacious beta(2)-agonists with similar log K(D) values (e.g. -9.57+/-0.15 and -10.04+/-0.096 respectively with salbutamol as agonist). 4 (3)H-CGP 12177 binding to beta(2)-adrenoceptors in intact CHO-beta(2) cells yielded a log K(D) value of -9.84+/-0.06, but indicated that the ligand dissociates very slowly from the receptor (t(1/2) for dissociation=65 min). However, studies with a Green Fluorescent Protein (GFP)-tagged beta(2)-adrenoceptor indicated that CGP 12177 does not stimulate beta(2)-adrenoceptor internalization. 5 This study demonstrates that CGP 12177 is a high affinity partial agonist of both cAMP accumulation and CRE-mediated gene transcription at the human beta(2)-adrenoceptor. It provides no evidence that CGP 12177 can discriminate a secondary site on the beta(2)-adrenoceptor analogous to that observed for the human beta(1)-adrenoceptor. However, despite its very weak actions on cAMP accumulation, the potent agonist effects of CGP 12177 on CRE-mediated gene transcription at the human beta(2)-adrenoceptor, coupled with its long duration of action, offers a potential lead for drug development for the treatment of chronic inflammatory airway diseases.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-10570045,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-10648634,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-10945842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-10952671,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-10960078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-11191841,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-11395153,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-11764780,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-11815381,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-12770923,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-1347503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-13651579,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-1479908,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-14907713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-1671733,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-1976019,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-2570569,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-2829922,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-2873196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-2876367,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-2891424,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-2893983,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-2993385,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-6131886,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-6143816,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-6315796,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-7881727,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-7938162,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-8104642,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-8771528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-8825348,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-9517390,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-9547357,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12237261-9831907
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-2 Receptor...,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Agonists,
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic beta-Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Alkaline Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/CGP 12177,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/Propanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/alkaline phosphatase, placental
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0007-1188
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
137
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
400-8
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:12237261-Adrenergic beta-2 Receptor Agonists,
pubmed-meshheading:12237261-Adrenergic beta-2 Receptor Antagonists,
pubmed-meshheading:12237261-Adrenergic beta-Agonists,
pubmed-meshheading:12237261-Adrenergic beta-Antagonists,
pubmed-meshheading:12237261-Alkaline Phosphatase,
pubmed-meshheading:12237261-Animals,
pubmed-meshheading:12237261-Binding, Competitive,
pubmed-meshheading:12237261-CHO Cells,
pubmed-meshheading:12237261-Cricetinae,
pubmed-meshheading:12237261-Cyclic AMP,
pubmed-meshheading:12237261-GPI-Linked Proteins,
pubmed-meshheading:12237261-Humans,
pubmed-meshheading:12237261-Isoenzymes,
pubmed-meshheading:12237261-Microscopy, Confocal,
pubmed-meshheading:12237261-Propanolamines,
pubmed-meshheading:12237261-Response Elements,
pubmed-meshheading:12237261-Transcription, Genetic
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
Pharmacological characterization of CGP 12177 at the human beta(2)-adrenoceptor.
|
|
pubmed:affiliation |
Institute of Cell Signalling, University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
