[Calcium signaling mediated by nicotine receptors in neurons].
Nicotine has many acute and chronic pharmacological effects. Nicotine treatment activates neuronal nicotinic acetylcholine receptors (nAChR) in peripheral and central nervous systems leading to depolarization and elevation of intracellular calcium levels, which are considered to cause stimulation of neurotransmitter release, synaptic transmission, intracellular signal transduction and gene expression. Multiple subtypes of nAChRs display different sensitivity to nicotinic agonists and antagonists. Each of these subtypes has a unique distribution in peripheral and central nervous systems. Although presynaptic nAChRs have been extensively studied to modulate the release of neurotransmitters, the functional importance of nAChRs in somata is not sufficiently characterized. To clarify the mechanisms of calcium signaling and its stimulation of gene expression via nAChRs in somata, we have investigated nAChR-mediating calcium signaling mechanisms including phosphorylation of p42/44 MAP kinase (ERK), CREB and Akt in PC12h cells. Nicotine transiently activates phosphorylation of ERK-, CREB and Akt. Nicotine induces the activation of both PI3 kinase/Act and ERK/CREB pathways via common pathways including non-alpha 7-nAChRs, L-type VSCC, CaM kinase and EGFR in PC12h cells, but Src family tyrosine kinases only participate in the pathway to activate Akt. Based on these results, we discuss nAChR signaling mechanisms in neurons.
Nakayama
Hitoshi
H
Department of Pharmacology, Nara Medical University, 840 Shijo-cho, Kashihara, 634-8521, Japan.
Nakashima
Toshikatu
T
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011978:Receptors, Nicotinic / Q000378:metabolism / Q000502:physiology*; D014415:Tunicamycin / Q000037:antagonists & inhibitors
D017362:Cyclic AMP Response Element-Binding Protein; D011518:Proto-Oncogene Proteins; D011978:Receptors, Nicotinic; D014415:Tunicamycin; D009538:Nicotine; D066246:ErbB Receptors; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1