Source:http://linkedlifedata.com/resource/pubmed/id/20236220
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
|
| pubmed:dateCreated |
2010-4-27
|
| pubmed:abstractText |
We investigated the regulatory pathways responsible for agonist-induced internalization and down-regulation of G(q) protein-coupled histamine H(1)-receptors in Chinese hamster ovary cells. Histamine-induced internalization and down-regulation of H(1)-receptors were detected as the loss of [(3)H]mepyramine binding sites on intact cells accessible to hydrophilic and hydrophobic H(1)-receptor antagonists, pirdonium and mepyramine, respectively. Pretreatment of cells with 0.1 mM histamine for 30 min at 37 degrees C induced internalization as well as down-regulation of H(1)-receptors, both of which were inhibited either in the presence of an inhibitor against G protein-coupled receptor kinases (ZnCl(2)) or under hypertonic conditions where clathrin-dependent endocytosis is known to be inhibited, but were not affected by inhibitors against caveolae/raft-dependent endocytosis (filipin and nystatin). Down-regulation of H(1)-receptors, but not their internalization, was inhibited by protein kinase C inhibitors (chelerythrin or GF109203X), a ubiquitin E1 inhibitor (UBEI-41) and proteasome inhibitors (lactacystin and MG-132). Neither a Ca(2+)/calmodulin-dependent protein kinase II inhibitor (KN-62) nor lysosomal protease inhibitors (E-64, leupeptin, chloroquine and NH(4)Cl) affected the internalization and down-regulation of H(1)-receptors. These results suggest that H(1)-receptors internalize upon agonist stimulation via G protein-coupled receptor kinase/clathrin-dependent but caveolae/raft-independent mechanisms and are delivered to proteasomes, preferentially to lysosomes, for their prompt down-regulation.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chlorides,
http://linkedlifedata.com/resource/pubmed/chemical/Clathrin,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Filipin,
http://linkedlifedata.com/resource/pubmed/chemical/G-Protein-Coupled Receptor Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Histamine,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Histamine H1,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Zinc Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/zinc chloride
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
May
|
| pubmed:issn |
1471-4159
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
113
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
990-1001
|
| pubmed:meshHeading |
pubmed-meshheading:20236220-Animals,
pubmed-meshheading:20236220-CHO Cells,
pubmed-meshheading:20236220-Chlorides,
pubmed-meshheading:20236220-Clathrin,
pubmed-meshheading:20236220-Cricetinae,
pubmed-meshheading:20236220-Cricetulus,
pubmed-meshheading:20236220-Down-Regulation,
pubmed-meshheading:20236220-Endocytosis,
pubmed-meshheading:20236220-Enzyme Inhibitors,
pubmed-meshheading:20236220-Filipin,
pubmed-meshheading:20236220-G-Protein-Coupled Receptor Kinase 1,
pubmed-meshheading:20236220-Histamine,
pubmed-meshheading:20236220-Proteasome Endopeptidase Complex,
pubmed-meshheading:20236220-Protein Kinase C,
pubmed-meshheading:20236220-Protein Transport,
pubmed-meshheading:20236220-Receptors, Histamine H1,
pubmed-meshheading:20236220-Transport Vesicles,
pubmed-meshheading:20236220-Ubiquitin,
pubmed-meshheading:20236220-Zinc Compounds
|
| pubmed:year |
2010
|
| pubmed:articleTitle |
Ubiquitin/proteasome-dependent down-regulation following clathrin-mediated internalization of histamine H1-receptors in Chinese hamster ovary cells.
|
| pubmed:affiliation |
Department of Pharmacodynamics, Meiji Pharmaceutical University, Tokyo, Japan. hishi@my-pharm.ac.jp
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|