Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-3
pubmed:dateCreated
2000-4-18
pubmed:abstractText
Human neuroblastoma SH-SY5Y cells express endogenous mu-opioid receptor and develop cellular tolerance to morphine after prolonged (>/=4 h) treatment with morphine. Treatment with forskolin (25 microM, 12 h), an adenylyl cyclase activator, also desensitized mu-opioid receptor response to morphine (10 microM) by 38% (P<0. 001), which was reversed by the cyclic AMP (cAMP) dependent kinase inhibitor N-(2-aminoethyl)-5-isoquinolinesulfonamide (H8) (100 microM). Treatment with both morphine and forskolin appeared to cause an additive effect in desensitizing mu-opioid receptor. In mu-opioid receptor stably transfected human embryonic kidney 293 (HEK-mu) cells, morphine treatment produced cAMP upregulation, yet failed to induce mu-opioid receptor tolerance. However, treatment with forskolin (25 microM) or 8-bromo-cAMP (1mM) led to profound mu-opioid receptor tolerance, which was reversed by H8. These results demonstrate that cAMP-dependent kinase activation causes mu-opioid receptor tolerance. However, morphine-induced mu-opioid receptor tolerance in SH-SY5Y cells is not mediated by cAMP-dependent kinase activation. In addition, our results indicate that cAMP-upregulation does not necessarily lead to mu-opioid receptor tolerance.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-2999
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
389
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
165-71
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Tolerance to morphine at the mu-opioid receptor differentially induced by cAMP-dependent protein kinase activation and morphine.
pubmed:affiliation
Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA. zwang@u.arizona.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.