Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2003-5-23
pubmed:abstractText
Morphine stimulates the internalization of mu-opioid receptors (MORs) in transfected cell models to a lesser degree than opioid peptides and other analgesic drugs, such as methadone, and previous studies have reported that morphine does not produce a detectable redistribution of MORs in neural tissue after either acute or chronic administration. Nevertheless, morphine produces profound physiological effects, raising the question of whether receptor trafficking plays any role in the in vivo actions of morphine. We investigated the effects of opiate drugs on recombinant and native opioid receptors in the nucleus accumbens, which plays an important role in mediating the behavioral effects of opiate drugs. Morphine and methadone differed in their effects on the internalization of epitope-tagged MORs in cell bodies, introduced by viral gene transfer and imaged by fluorescence microscopy. A mutation of the cytoplasmic tail that confers morphine-induced internalization in cultured cells had a similar effect on receptor trafficking in nucleus accumbens cell bodies. Surprisingly, in contrast to its failure to affect MOR distribution detectably in cell bodies, acute morphine administration produced a pronounced change in MOR distribution visualized in the processes of the same neurons. A similar effect of acute morphine administration was observed for endogenously expressed MORs by immunoelectron microscopy; the acute administration of morphine increased the density of MORs associated with internal membrane structures specifically in dendrites. These results provide the first evidence that morphine regulates the distribution of MORs in neuronal processes, suggesting that "compartment-selective" membrane trafficking represents a previously unanticipated type of opioid receptor regulation contributing to the in vivo effects of opiate drugs on a physiologically relevant population of CNS neurons.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4324-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12764121-Animals, pubmed-meshheading:12764121-Dendrites, pubmed-meshheading:12764121-Endocytosis, pubmed-meshheading:12764121-Genetic Vectors, pubmed-meshheading:12764121-Injections, Intraperitoneal, pubmed-meshheading:12764121-Injections, Subcutaneous, pubmed-meshheading:12764121-Male, pubmed-meshheading:12764121-Membrane Proteins, pubmed-meshheading:12764121-Methadone, pubmed-meshheading:12764121-Morphine, pubmed-meshheading:12764121-Mutation, pubmed-meshheading:12764121-Neurons, pubmed-meshheading:12764121-Nucleus Accumbens, pubmed-meshheading:12764121-Protein Transport, pubmed-meshheading:12764121-Rats, pubmed-meshheading:12764121-Rats, Sprague-Dawley, pubmed-meshheading:12764121-Receptors, Opioid, delta, pubmed-meshheading:12764121-Receptors, Opioid, mu, pubmed-meshheading:12764121-Recombinant Proteins, pubmed-meshheading:12764121-Simplexvirus
pubmed:year
2003
pubmed:articleTitle
Morphine acutely regulates opioid receptor trafficking selectively in dendrites of nucleus accumbens neurons.
pubmed:affiliation
Department of Psychiatry, University of California, San Francisco, San Francisco, California 94143-2140, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.