Linked Life Data

21849544

Source:http://linkedlifedata.com/resource/pubmed/id/21849544

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2011-8-18
pubmed:abstractText
We previously demonstrated that the spinal cord ?-opioid receptor (KOR) and ?-opioid receptor (MOR) form heterodimers (KOR/MOR). KOR/MOR formation and the associated KOR dependency of spinal morphine antinociception are most robust during proestrus. Using Sprague Dawley rats, we now demonstrate that (1) spinal synthesis of estrogen is critical to these processes, and (2) blockade of either estrogen receptor (ER) ?-, ?-, or G-protein-coupled ER1 or progesterone receptor (PR) substantially reduces KOR/MOR and eliminates mediation by KOR of spinal morphine antinociception. Effects of blocking ERs were manifest within 15 min, whereas those of PR blockade were manifest after 18 h, indicating the requirement for rapid signaling by estrogen and transcriptional effects of progesterone. Individual or combined blockade of ERs produced the same magnitude of effect, suggesting that they work in tandem as part of a macromolecular complex to regulate KOR/MOR formation. Consistent with this inference, we found that KOR and MOR were coexpressed with ER? and G-protein-coupled ER1 in the spinal dorsal horn. Reduction of KOR/MOR by ER or PR blockade or spinal aromatase inhibition shifts spinal morphine antinociception from KOR dependent to KOR independent. This indicates a sex steroid-dependent plasticity of spinal KOR functionality, which could explain the greater analgesic potency of KOR agonists in women versus men. We suggest that KOR/MOR is a molecular switch that shifts the function of KOR and thereby endogenous dynorphin from pronociceptive to antinociceptive. KOR/MOR could thus serve as a novel molecular target for pain management in women.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
17
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
11836-45
pubmed:meshHeading
pubmed-meshheading:21849544-Animals, pubmed-meshheading:21849544-Aromatase, pubmed-meshheading:21849544-Estrogen Antagonists, pubmed-meshheading:21849544-Estrogen Receptor alpha, pubmed-meshheading:21849544-Estrogen Receptor beta, pubmed-meshheading:21849544-Estrogens, pubmed-meshheading:21849544-Female, pubmed-meshheading:21849544-Injections, Spinal, pubmed-meshheading:21849544-Morphine, pubmed-meshheading:21849544-Pain, pubmed-meshheading:21849544-Pain Measurement, pubmed-meshheading:21849544-Posterior Horn Cells, pubmed-meshheading:21849544-Protein Multimerization, pubmed-meshheading:21849544-Rats, pubmed-meshheading:21849544-Rats, Sprague-Dawley, pubmed-meshheading:21849544-Receptors, Estrogen, pubmed-meshheading:21849544-Receptors, Opioid, kappa, pubmed-meshheading:21849544-Receptors, Opioid, mu, pubmed-meshheading:21849544-Sex Factors, pubmed-meshheading:21849544-Signal Transduction, pubmed-meshheading:21849544-Spinal Cord
pubmed:year
2011
pubmed:articleTitle
Spinal synthesis of estrogen and concomitant signaling by membrane estrogen receptors regulate spinal ?- and ?-opioid receptor heterodimerization and female-specific spinal morphine antinociception.
pubmed:affiliation
State University of New York, Downstate Medical Center, Brooklyn, New York 11203, USA.
pubmed:publicationType
Journal Article, Comparative Study