Nicotine‐induced phosphorylation of ERK in mouse primary cortical neurons: evidence for involvement of glutamatergic signaling and CaMKII

摘要: Extracellular signal-regulated kinase (ERK) is activated in vivo a number of brain areas by nicotine and other drugs abuse. Here we show that stimulation cultured mouse cortical neurons leads to robust induction ERK phosphorylation dependent on concentration duration exposure. Calcium/calmodulin-dependent protein II activity necessary for nicotine-induced neither cAMP-dependent or C appear be involved. Activity glutamate receptors, L-type voltage-gated calcium channels, sodium channels are also required phosphorylation. Nicotine-induced was inhibited high concentrations mecamylamine, however it not blocked broad nicotinic acetylcholine receptor (nAChR) inhibitors (including hexamethonium chlorisondamine) nAChR subtype selective (such as methyllycaconitine, alpha-bungarotoxin, dihydro-beta-erythroidine, α-conotoxin Au1B). In accord with these pharmacological results, normal primary cultures made from β2 α7 subunit knockout mice. The α3/beta4 agonist cytisine did induce suggesting α3/β4 nAChRs were involved this process. Taken together, data define role glutamatergic signaling calcium/calmodulin-dependent do provide evidence the involvement classical nAChRs.