Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion in adrenal chromaffin cells

Yokoo, Hiroki; Shiraishi, Seiji; Kobayashi, Hideyuki; Yanagita, Toshihiko; Minami, Shin-ichi; Yamamoto, Ryōichi; Wada, Akihiko

doi:10.1016/s0006-8993(00)02492-6

Cited by 4 publications

(2 citation statements)

References 39 publications

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“…Nicotine can cause intracellular Na ϩ influx via cation-channel-coupled nicotinic acetylcholine receptors during depolarization of the cell membrane, and as a result can cause Ca 2ϩ influx via voltage dependent Ca 2ϩ channels. 12,13) However, in the present study SEA0400 had no effect on nicotine-induced convulsions. Taken together, our data suggest that the mechanism of PTZ-induced expression and action of convulsion is very complex, but Ca 2ϩ influx via NCX seem to be important.…”

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confidence: 77%

Involvement of Na+/Ca2+ Exchanger in Pentylenetetrazol-Induced Convulsion by Use of Na+/Ca2+ Exchanger Knockout Mice

Saito

Kaneko

Tanaka

et al. 2009

Biological & Pharmaceutical Bulletin

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Epilepsy is a common psychiatric disorder, and in the last decade, genetic abnormalities of genes encoding ion channels expressed in the brain have been identified as the cause of twenty idiopathic epilepsy syndromes. We have already reported that nicotinic acetylcholine receptor mutation exhibit the nocturnal frontal lobe epilepsy phenotype in rats. 1)Experimentally, numerous studies also suggest that ion channels, in particular Ca 2ϩ or K ϩ channels, are involved in epilepsy; however, the detailed mechanisms are unclear. The Na ϩ /Ca 2ϩ exchanger (NCX) is a cell-membrane ion transporter which plays an important role in regulation of intracellular Ca 2ϩ levels. In the central nervous system (CNS), NCX has been classified into three types of isoforms; NCX1, NCX2, and NCX3. NCX1 is expressed at high levels in the brain, the heart, and the kidney, while NCX2 and NCX3 are mainly expressed at high levels in the brain and in skeletal muscles.2,3) Recently, a potent and selective NCX enzyme inhibitor, 2-[4-[(2,5)-difluoro-phenyl]methoxy]-5-ethoxyaniline (SEA0400) has been developed, 4) and has been reported to provide protection in models of cerebral ischemia and reperfusion injury after ischemia. 5,6) However, the effect of NCX on epilepsy has not been reported.In the present study, therefore, we examined the involvement of NCX in drug-induced convulsions in mice using either the NCX inhibitor SEA0400 or NCX knockout mice.In the present study, ddY-male mice weighing 25-35 g were used. The animals were maintained at 24Ϯ2°C with a 12 h light-dark cycle, and were given free access to commercial food and tap water. The NCX inhibitor SEA0400 (2 mg/kg, per os (p.o.); SEA0400 group) or vehicle (20% soy bean oil; control group) was administered to mice at 45 min prior to either pentylenetetrazol (PTZ 60 mg/kg, intraperitoneally (i.p.); nϭ7 and 6, respectively; Sigma), bicuculline (5 mg/kg, i.p.; nϭ8 and 9, respectively; Sigma), nicotine (6 mg/kg, i.p.; nϭ5 and 3, respectively; Wako), or 4-aminopyridine (10 mg/kg, i.p.; nϭ5 for both groups; Sigma) for induction of different types of seizures. The appropriate dose of each drug was examined by checking dosage dependence in advance, ensuring that it was not a lethal dose but an adequate one to cause convulsions. However, the convulsions induced by each drug were not in the same way. Therefore, we examined tail reaction, clonic convulsion, tonic flexion, tonic extension convulsion, and the reaction in the case of PTZ, bicuculline, and 4-aminopyridine. In the case of nicotine, appearance, latency and duration of wild running were added. Clonic convulsions were determined by the occurrence of rhythmical repeated muscle contractions of the limbs of the mice, and the disappearance of the righting reflex for more than 3 s.NCX1 knockout mice were prepared as previously described, 7) and housed as for ddY-male mice. These mice received pentylenetetrazol (PTZ 40 mg/kg, i.p.), bicuculline (5 mg/kg, i.p.), nicotine (6 mg/kg, i.p.), or 4-aminopyridine (10 mg/kg, i.p.) for induction of seizu...

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confidence: 77%

Involvement of Na+/Ca2+ Exchanger in Pentylenetetrazol-Induced Convulsion by Use of Na+/Ca2+ Exchanger Knockout Mice

Saito

Kaneko

Tanaka

et al. 2009

Biological & Pharmaceutical Bulletin

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“…Secretion and transcription of catecholamines upon nicotinic cholinergic activation are triggered by sodium entry followed by a transient calcium influx that is mediated by voltage gated calcium channels (VGCCs; [194]). Nicotine also induces a dose-dependent increase in the intracellular calcium concentration [Ca ++ ] i via increasing calcium influx from extracellular space, and activating inositol(1,4,5)-trisphosphate (IP3) receptor-coupled intracellular calcium reserves.…”

Section: Signaling Pathways Involved In Catecholamine Synthesis and Rmentioning

confidence: 99%

Nicotine, Body Weight and Potential Implications in the Treatment of Obesity

Kane²,

Konu³

2003

CTMC

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Obesity is an epidemic problem in the U. S. and many other industrialized nations. Historically, the drugs used for the treatment of obesity generally targeted small molecule neurotransmitters. As research grows to decipher the underlying molecular mechanisms behind energy homeostasis, it is becoming evident that the modulating effects of neuropeptides also are critical in the regulation of appetite and metabolism. The search for drugs to modify these monoaminergic and peptidergic pathways may eventually prove successful in the treatment of obesity. While tobacco smoking has long been used as one strategy to maintain a lower body weight, especially in female smokers, its adverse associations with addiction and disease overshadow its potential use as an antiobesity agent. Potential pharmacological effects of nicotine could be better understood as the intricacies of the nicotinic acetylcholine receptor are revealed. The objective of this review is threefold: first is to provide an overview of the physiological effects of nicotine on body weight while focusing on the drugs that are available as antiobesity and smoking cessation agents. Second is to provide the present status of the nicotinic acetylcholine receptor as it relates to energy homeostasis and its potential as an effective treatment modality for obesity. Third is to present the current knowledge with respect to nicotine's effects on energy homeostatic and reward related pathways at the molecular level. A better understanding of the regulatory mechanisms underlying the pharmacological effects of nicotine on body weight will provide insights in identification of potential targets for the development of appropriate medicines in the treatment of obesity.

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Chromaffin cells as a model to evaluate mechanisms of cell death and neuroprotective compounds

Rı́os

Cano‐Abad

Villarroya

et al. 2017

Pflugers Arch - Eur J Physiol

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In this review, we show how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action. Chromaffin cells are considered paraneurons, as they share many common features with neurons: (i) they synthesize, store, and release neurotransmitters upon stimulation and (ii) they express voltage-dependent calcium, sodium, and potassium channels, in addition to a wide variety of receptors. All these characteristics, together with the fact that primary cultures from bovine adrenal glands or chromaffin cells from the tumor pheochromocytoma cell line PC12 are easy to culture, make them an ideal model to study neurotoxic mechanisms and neuroprotective drugs. In the first part of this review, we will analyze the different cytotoxicity models related to calcium dyshomeostasis and neurodegenerative disorders like Alzheimer's or Parkinson's. Along the second part of the review, we describe how different classes of drugs have been evaluated in chromaffin cells to determine their neuroprotective profile in different neurodegenerative-related models.

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Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion in adrenal chromaffin cells

Cited by 4 publications

References 39 publications

Involvement of Na+/Ca2+ Exchanger in Pentylenetetrazol-Induced Convulsion by Use of Na+/Ca2+ Exchanger Knockout Mice

Involvement of Na+/Ca2+ Exchanger in Pentylenetetrazol-Induced Convulsion by Use of Na+/Ca2+ Exchanger Knockout Mice

Nicotine, Body Weight and Potential Implications in the Treatment of Obesity

Chromaffin cells as a model to evaluate mechanisms of cell death and neuroprotective compounds

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