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Role of δ‐opioid receptor function in neurogenesis and neuroprotection
Author(s) -
Narita Minoru,
Kuzumaki Naoko,
Miyatake Mayumi,
Sato Fumiaki,
Wachi Hiroshi,
Seyama Yoshiyuki,
Suzuki Tsutomu
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03849.x
Subject(s) - neurogenesis , neuroprotection , δ opioid receptor , neuroscience , opioid , receptor , pharmacology , medicine , biology
The present study was undertaken to evaluate the implication of δ‐opioid receptor function in neurogenesis and neuroprotection. We found that the stimulation of δ‐opioid receptors by the selective δ‐opioid receptor agonist SNC80 [(+)‐4‐[(α R )‐α‐((2 S ,5 R )‐4‐allyl‐2,5‐dimethyl‐1‐piperazinyl)‐3‐methoxybenzyl]‐ N , N ‐diethylbenzamide] (10 n m ) promoted neural differentiation from multipotent neural stem cells obtained from embryonic C3H mouse forebrains. In contrast, either a selective µ‐opioid receptor agonist, [ d ‐Ala 2 , N ‐Me‐Phe 4 , Gly 5 ‐ol]‐enkephalin (DAMGO), or a specific κ‐opioid receptor agonist, (–)‐ trans ‐(1 S ,2 S )‐U‐50488 hydrochloride (U50,488H), had no such effect. In addition to neural differentiation, the increase in cleaved caspase 3‐like immunoreactivity induced by H 2 O 2 (3 µ m ) was suppressed by treatment with SNC80 in cortical neuron/glia co‐cultures. These effects of SNC80 were abolished by a Trk‐dependent tyrosine kinase inhibitor: (8 R *,9 S *,11 S *)‐(–)‐9‐hydroxy‐9‐methoxycarbonyl‐8‐methyl‐2,3,9,10‐tetrahydro‐8,11‐epoxy‐1 H ,8 H ,11 H ‐2,7b,11a‐triazadibenzo(a,g)cycloocta(cde)trinden‐1‐one (K‐252a). The SNC80‐induced neural differentiation was also inhibited by treatment with the protein kinase C (PKC) inhibitor, phosphatidylinositol 3‐kinase (PI3K) inhibitor, mitogen‐activated protein kinase kinase (MEK) inhibitor or Ca 2+ /calmodulin‐dependent protein kinase II (CaMKII) inhibitor. These findings raise the possibility that δ‐opioid receptors play a crucial role in neurogenesis and neuroprotection, mainly through the activation of Trk‐dependent tyrosine kinase, which could be linked to PI3K, PKC, CaMKII and MEK.