Linked Life Data

11146127

Source:http://linkedlifedata.com/resource/pubmed/id/11146127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2001-1-26
pubmed:abstractText
The mu-opioid receptor (MOR1) mediates the main analgesic effects of morphine and several other opioids. However, the clinical benefit of these drugs is limited by the development of tolerance and dependence. In vitro the mu-opioid receptor undergoes a rapid homologous desensitization during prolonged agonist exposure. We have recently identified the serine residues, Ser(261) and Ser(266), within the third intracellular loop as two consensus calcium/calmodulin-dependent protein kinase II (CaMKII) sites required for agonist-induced phosphorylation and desensitization of the mu-opioid receptor in HEK 293 cells. Since the specific pattern of mu-opioid receptor regulation in vivo is thought to depend on the cell- and tissue-specific complement of protein kinases, we examined the spatial relation between MOR1 and CaMKII in rat brain using specific antibodies. We found that MOR1 and CaMKII alpha which is a major CaMKII isoform expressed in the central nervous system co-exist in distinct pain-processing brain regions including the superficial layers of the spinal cord dorsal horn and dorsal root ganglia. At high power magnification it was evident that virtually all MOR1-expressing nociceptive spinal cord neurons also co-contain CaMKII. In naive or saline-treated animals the mu-opioid receptor was almost exclusively confined to the plasma membrane, while CaMKII was localized to vesicle-like structures throughout the cytoplasm. After subcutaneous administration of the mu-opioid receptor agonist, etorphine, a large proportion of the mu-opioid receptor proteins redistributed from the plasma membrane into the cytosol where it was frequently co-localized with CaMKII. Together, we identify CaMKII as a potential protein kinase, which by virtue of its colocalization with MOR1 may be in a position to phosphorylate the mu-opioid receptor and may thus contribute to the development of tolerance to opioid analgesics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
85
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
239-50
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Colocalization of the mu-opioid receptor and calcium/calmodulin-dependent kinase II in distinct pain-processing brain regions.
pubmed:affiliation
Department of Pharmacology and Toxicology, Otto-von-Guericke University, Leipziger Str. 44, Magdeburg 39120, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't