Involvement of α7- and α4β2-type postsynaptic nicotinic acetylcholine receptors in nicotine-induced excitation of dopaminergic neurons in the substantia nigra: a patch clamp and single-cell PCR study using acutely dissociated nigral neurons

Matsubayashi, Hiroaki; Inoue, Atsuko; Amano, Taku; Seki, Takahiro; Nakata, Yoshihiro; Sasa, Masashi; Sakai, Norio

doi:10.1016/j.molbrainres.2004.06.040

Cited by 39 publications

(38 citation statements)

References 15 publications

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“…Among the homomeric type, only ␣7 receptors are widely distributed in the mammalian central nervous system. Matsubayashi et al (2004) revealed that mRNA for ␣7 nicotinic receptor subunit and TH were detected in the same single neuron in substantia nigra, suggesting that activation of postsynaptic ␣7 (and also ␣4-␤2) nAChR in this area results in the excitation of dopaminergic neurons.…”

Section: Discussionmentioning

confidence: 96%

Methyllycaconitine Prevents Methamphetamine-Induced Effects in Mouse Striatum: Involvement of α7 Nicotinic Receptors

Escubedo

Chipana²,

Pérez-Sánchez³

et al. 2005

J Pharmacol Exp Ther

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In a previous study, we demonstrated that in rat striatal synaptosomes, methamphetamine (METH)-induced reactive oxygen species (ROS) production was prevented by methyllycaconitine (MLA), a specific antagonist of ␣7 neuronal nicotinic acetylcholine receptors (␣7 nAChR). The aim of this study was to test the influence of MLA on acute METH effects and neurotoxicity in mice, using both in vivo and in vitro models. MLA inhibited METH-induced climbing behavior by 50%. Acute effects after 30-min preincubation with 1 M METH also included a decrease in striatal synaptosome dopamine (DA) uptake, which was prevented by MLA. METH-induced neurotoxicity was assessed in vivo in terms of loss of striatal dopaminergic terminals (73%) and of tyrosine hydroxylase levels (by 90%) at 72 h post-treatment, which was significantly attenuated by MLA. Microglial activation [measured as 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide binding] was also present at 24 h post-treatment and was fully prevented by MLA, tending to confirm its neuroprotective activity. MLA had no effect on METH-induced hyperthermia. Additionally, flow cytometry assays showed that METH-induced ROS generation occurs inside synaptosomes from mouse striatum. This effect implied release of vesicular DA and was calcium-, neuronal nitric-oxide synthase-, and protein kinase C-dependent. MLA and ␣-bungarotoxin, but not dihydro-␤-erythroidine (an antagonist that blocks nAChR-containing ␤2 subunits), fully prevented METH-induced ROS production without affecting vesicular DA uptake. The importance of this study lies not only in the neuroprotective effect elicited by the blockade of the ␣7 nicotinic receptors by MLA but also in that it proposes a new mechanism with which to study METH-induced acute and longterm effects.

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Section: Discussionmentioning

confidence: 96%

Methyllycaconitine Prevents Methamphetamine-Induced Effects in Mouse Striatum: Involvement of α7 Nicotinic Receptors

Escubedo

Chipana²,

Pérez-Sánchez³

et al. 2005

J Pharmacol Exp Ther

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“…Results from in vitro experiments suggest that malignant growth can be halted with the use of snake neurotoxins (a-neurotoxins) or snail conotoxins (a-conotoxins) (75,76) because they are competitive antagonists of a7-nAChR (77). In vivo animal studies have further shown that a7-nAChR inhibitors, such as MLA (78,79) and a-Bgtx (80), can reverse the proangiogenic effects of nicotine and inhibit cancer cell growth (16,17,19,81,82). In a lung airway epithelial cell model (83), normal human bronchial epithelial (NHBE) cells were forced to transform by nicotinic activation of Akt, altering their growth characteristics.…”

Section: Nachr Antagonists As Potential Agents For Molecular Cancer Tmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

103

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The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and a-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that a9-nAChR is important for breast cancer formation, and in many in vivo studies, a9-nAChR-specific antagonists (e.g., a-ImI, a-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine-and estrogeninduced breast cancer cell proliferation through inhibition of the a9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation.

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“…In previous years, several reports documented the biological effect of nicotine on DCs and macrophages [29,[52][53][54][55][56] . Nicotine has been reported to decrease levels of proinflammatory cytokines and reduce the ability of T-cell priming [54,57] , but has also been described to enhance the costimulatory molecular expression in DCs and facilitate T-cell priming [53] .…”

Section: Nicotine and Immunitymentioning

confidence: 99%

Nicotine and inflammatory neurological disorders

et al. 2009

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Cigarette smoke is a major health risk factor which significantly increases the incidence of diseases including lung cancer and respiratory infections. However, there is increasing evidence that smokers have a lower incidence of some inflammatory and neurodegenerative diseases. Nicotine is the main immunosuppressive constituent of cigarette smoke, which inhibits both the innate and adaptive immune responses. Unlike cigarette smoke, nicotine is not yet considered to be a carcinogen and may, in fact, have therapeutic potential as a neuroprotective and anti-inflammatory agent. This review provides a synopsis summarizing the effects of nicotine on the immune system and its (nicotine) influences on various neurological diseases.

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Involvement of α7- and α4β2-type postsynaptic nicotinic acetylcholine receptors in nicotine-induced excitation of dopaminergic neurons in the substantia nigra: a patch clamp and single-cell PCR study using acutely dissociated nigral neurons

Cited by 39 publications

References 15 publications

Methyllycaconitine Prevents Methamphetamine-Induced Effects in Mouse Striatum: Involvement of α7 Nicotinic Receptors

Methyllycaconitine Prevents Methamphetamine-Induced Effects in Mouse Striatum: Involvement of α7 Nicotinic Receptors

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Nicotine and inflammatory neurological disorders

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