| pubmed-article:12873944 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0010453 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0013935 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0027882 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0019564 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0597357 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0079883 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0439852 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0066815 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C2603343 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0127400 | lld:lifeskim |
| pubmed-article:12873944 | lifeskim:mentions | umls-concept:C0598002 | lld:lifeskim |
| pubmed-article:12873944 | pubmed:issue | 2 | lld:pubmed |
| pubmed-article:12873944 | pubmed:dateCreated | 2003-7-22 | lld:pubmed |
| pubmed-article:12873944 | pubmed:abstractText | Indirect evidence indicates that morphine-3-glucuronide (M3G) may contribute significantly to the neuro-excitatory side effects (myoclonus and allodynia) of large-dose systemic morphine. To gain insight into the mechanism underlying M3G's excitatory behaviors, we used fluo-3 fluorescence digital imaging techniques to assess the acute effects of M3G (5-500 microM) on the cytosolic calcium concentration ([Ca(2+)](CYT)) in cultured embryonic hippocampal neurones. Acute (3 min) exposure of neurones to M3G evoked [Ca(2+)](CYT) transients that were typically either (a) transient oscillatory responses characterized by a rapid increase in [Ca(2+)](CYT) oscillation amplitude that was sustained for at least approximately 30 s or (b) a sustained increase in [Ca(2+)](CYT) that slowly recovered to baseline. Naloxone-pretreatment decreased the proportion of M3G-responsive neurones by 10%-25%, implicating a predominantly non-opioidergic mechanism. Although the naloxone-insensitive M3G-induced increases in [Ca(2+)](CYT) were completely blocked by N-methyl-D-aspartic acid (NMDA) antagonists and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate antagonist), CNQX did not block the large increase in [Ca(2+)](CYT) evoked by NMDA (as expected), confirming that M3G indirectly activates the NMDA receptor. Additionally, tetrodotoxin (Na(+) channel blocker), baclofen (gamma-aminobutyric acid(B) agonist), MVIIC (P/Q-type calcium channel blocker), and nifedipine (L-type calcium channel blocker) all abolished M3G-induced increases in [Ca(2+)](CYT), suggesting that M3G may produce its neuro-excitatory effects by modulating neurotransmitter release. However, additional characterization is required. IMPLICATIONS: Large systemic doses of morphine administered to some patients for cancer pain management have been reported to produce myoclonus and allodynia. Indirect evidence implicates the major morphine metabolite, morphine-3-glucuronide (M3G), in these neuro-excitatory side effects. Hence, this study was designed to gain insight into the cellular mechanism responsible for M3G's neuro-excitatory actions. | lld:pubmed |
| pubmed-article:12873944 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12873944 | pubmed:language | eng | lld:pubmed |
| pubmed-article:12873944 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:12873944 | pubmed:citationSubset | AIM | lld:pubmed |
| pubmed-article:12873944 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:12873944 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:12873944 | pubmed:month | Aug | lld:pubmed |
| pubmed-article:12873944 | pubmed:issn | 0003-2999 | lld:pubmed |
| pubmed-article:12873944 | pubmed:author | pubmed-author:SmithDeborahD | lld:pubmed |
| pubmed-article:12873944 | pubmed:author | pubmed-author:SmithMaree... | lld:pubmed |
| pubmed-article:12873944 | pubmed:author | pubmed-author:MonteithGrego... | lld:pubmed |
| pubmed-article:12873944 | pubmed:author | pubmed-author:HemstapatKamo... | lld:pubmed |
| pubmed-article:12873944 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:12873944 | pubmed:volume | 97 | lld:pubmed |
| pubmed-article:12873944 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:12873944 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:12873944 | pubmed:pagination | 494-505, table of contents | lld:pubmed |
| pubmed-article:12873944 | pubmed:dateRevised | 2006-11-15 | lld:pubmed |
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| pubmed-article:12873944 | pubmed:year | 2003 | lld:pubmed |
| pubmed-article:12873944 | pubmed:articleTitle | Morphine-3-glucuronide's neuro-excitatory effects are mediated via indirect activation of N-methyl-D-aspartic acid receptors: mechanistic studies in embryonic cultured hippocampal neurones. | lld:pubmed |
| pubmed-article:12873944 | pubmed:affiliation | School of Pharmacy, The University of Queensland, St Lucia Campus, Brisbane, Australia. | lld:pubmed |
| pubmed-article:12873944 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:12873944 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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