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Morphine upregulates functional expression of neurokinin‐1 receptor in neurons
Author(s) -
Wan Qi,
Douglas Steven D.,
Wang Xu,
Kolson Dennis L.,
O'Donnell Lauren A.,
Ho WenZhe
Publication year - 2006
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21053
Subject(s) - morphine , dynorphin , tachykinin receptor 1 , opioid , receptor , opioid receptor , substance p , neuropeptide , pharmacology , naltrexone , chemistry , opioid peptide , medicine , biology
Abstract Neuronkinin‐1 receptor (NK‐1R), the neuropeptide substance P (SP) preferring receptor, is highly expressed in areas of the central nervous system (CNS) that are especially implicated in depression, anxiety, and stress. Repeated exposure to opioids may sensitize neuronal systems involved in stress response. We examined the effects of morphine, the principal metabolite of heroin, on the functional expression of NK‐1R in the cortical neurons. NK‐1R and mu‐opioid receptor (MOR) are co‐expressed in the cortical neurons. Morphine enhanced NK‐1R expression in the cortical neurons at both the mRNA and protein levels. The upregulated NK‐1R by morphine had functional activity, because morphine‐treated cortical neurons had greater SP‐induced Ca 2+ mobilization than untreated neurons. Blocking opioid receptors on the cortical neurons by naltrexone or CTAP (a μ‐opioid receptor antagonist) abolished the morphine action. Investigation of the mechanism(s) responsible for the morphine action showed that morphine activated NK‐1R promoter and induced the phosphorylation of p38 MAPK protein in the cortical neurons. These in vitro data provide a plausible cellular mechanism for opioid‐mediated neurological disorders. © 2006 Wiley‐Liss, Inc.