Desnitro-imidacloprid activates the extracellular signal-regulated kinase cascade via the nicotinic receptor and intracellular calcium mobilization in N1E-115 cells.
Desnitro-imidacloprid activates the extracellular signal-regulated kinase cascade via the nicotinic receptor and intracellular calcium mobilization in N1E-115 cells.
复制标题
Desnitro-imidacloprid 通过 N1E-115 细胞中的烟碱受体和细胞内钙动员激活细胞外信号调节激酶级联。
DOI：
10.1006/taap.2002.9503
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发表时间：
2002
影响因子：
3.8
通讯作者：
Casida,JohnE
中科院分区：
文献类型：
--
作者：
Tomizawa,Motohiro;Casida,JohnE
Imidacloprid (IMI) is the principal neonicotinoid (the only major new class of synthetic insecticides of the past three decades). The excellent safety profile of IMI is not shared with a metabolite, desnitro-IMI (DNIMI), which displays high toxicity to mammals associated with agonist action at the α4β2 nicotinic acetylcholine receptor (nAChR) in brain. This study examines the hypothesis that IMI, DNIMI, and (−)-nicotine activate the extracellular signal-regulated kinase (ERK) cascade via primary interaction with the α4β2 nAChR in mouse neuroblastoma N1E-115 cells. These three nicotinic agonists induce phosphorylation of ERK (p44/p42) in a concentration-dependent manner with an optimal incubation period of 30 min. DNIMI (1 μM)-induced ERK activation is blocked by nicotinic antagonist mecamylamine but not by α-bungarotoxin and muscarinic antagonist atropine. This activation is prevented by intracellular Ca2+chelator BAPTA-AM but not by removal of external Ca2+using EGTA and Ca2+-free medium. 2-Aminoethoxy-diphenylborate, a blocker for inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+release from intracellular stores, inhibits DNIMI-induced ERK activation but a high level of ryanodine (to block ryanodine receptor-mediated Ca2+release) does not. The inhibitor U-73122 for phospholipase C (to suppress IP3production) prevents ERK activation evoked by DNIMI. Inhibitors for protein kinase C (PKC) (GF109203X) and ERK kinase (PD98059) block this activation whereas an inhibitor (H-89) for cyclic AMP-dependent protein kinase does not. Thus, neonicotinoids activate the ERK cascade triggered by primary action at the α4β2 nAChR with an involvement of intracellular Ca2+mobilization possibly mediated by IP3. It is further suggested that intracellular Ca2+activates a sequential pathway from PKC to ERK.
