Epibatidine: a nicotinic acetylcholine receptor agonist releases monoaminergic neurotransmitters: in vitro and in vivo evidence in rats.
Epibatidine: a nicotinic acetylcholine receptor agonist releases monoaminergic neurotransmitters: in vitro and in vivo evidence in rats.
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Epibatidine：烟碱乙酰胆碱受体激动剂释放单胺能神经递质：大鼠体外和体内证据。
DOI：
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发表时间：
1996
影响因子：
3.5
通讯作者：
G. Lloyd
中科院分区：
文献类型：
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作者：
Aida I. Sacaan;F. Menzaghi;J. Dunlop;Lucia Correa;Kevin T. Whelan;G. Lloyd
研究了神经元乙酰胆碱门控离子通道受体激动剂（+/-）-地棘蛙素对体外神经递质释放和体内运动行为的影响。（+/-）-Epibatidine（3-300 nM）引起纹状体切片中[3 H]-多巴胺的浓度和钙依赖性释放以及海马和丘脑切片中[3 H]-去甲肾上腺素的释放。（+/-）-表巴替啶诱导的神经递质释放在所有三个区域被美加明（3 μ M）抑制。相比之下，D-筒箭毒碱（10-100 μ M）仅抑制（+/-）-epibatidine诱导的[3 H]-去甲肾上腺素从海马和丘脑释放。相反，二氢β-赤藓定（3-100 μ M）抑制纹状体中（+/-）-epibatidine诱导的[3 H]-多巴胺释放，而不显著改变海马或丘脑中[3 H]-去甲肾上腺素的释放。这与观察结果一致，即与去甲肾上腺素释放相比，不同的nAChR调节多巴胺释放。（+/-）-地棘蛙素对[3 H]-多巴胺和[3 H]-去甲肾上腺素释放的影响是河豚毒素敏感的，表明钠通道的参与。（+/-）-地棘蛙素（1-3微克/千克皮下注射）在单侧[6（OH）-DA]损伤的大鼠中产生同侧转动。（-）-尼古丁（0.35 mg/kg s.c.）模拟了该效应。美加明（3 mg/kg s.c.）可显著抑制（+/-）-地棘蛙素和（-）-尼古丁诱导的翻转，表明转向反应是由nAChRs介导的。（+/-）-地棘蛙素还以剂量依赖性方式增加运动活性。D1和D2受体拮抗剂SCH 23390和依替氯必利分别阻断了（+/-）-地棘蛙肽诱导的活动过度，表明（+/-）-地棘蛙肽的运动效应可能需要两种多巴胺受体亚型。这些结果表明，（+/-）-地棘蛙素在大鼠CNS中显示nAChR激动剂活性，并且某些作用是通过nAChR刺激的儿茶酚胺释放和随后相应受体的激活介导的。
The effect of the neuronal acetylcholine-gated ion channel receptor agonist (+/-)-epibatidine was studied on neurotransmitter release in vitro and motor behavior in vivo. (+/-)-Epibatidine (3-300 nM) caused a concentration- and calcium-dependent release of [3H]-dopamine from striatal slices and [3H]-norepinephrine release from hippocampal and thalamic slices. (+/-)-Epibatidine-induced neurotransmitter release was inhibited in all three regions by mecamylamine (3 microM). In contrast, D-tubocurarine (10-100 microM) inhibited only (+/-)-epibatidine-induced [3H]-norepinephrine release from the hippocampus and the thalamus. Conversely, dihydro beta-erythroidine (3-100 microM) inhibited (+/-)-epibatidine-induced [3H]-dopamine release in the striatum without significantly altering [3H]-norepinephrine release from either the hippocampus or the thalamus. This is consistent with the observation that different nAChRs modulate dopamine release as compared with norepinephrine release. The effect of (+/-)-epibatidine on both [3H]-dopamine and [3H]-norepinephrine release was tetrodotoxin-sensitive, suggesting the involvement of sodium channels. (+/-)-Epibatidine (1-3 micrograms/kg s.c.) produced ipsilateral turning in the unilaterally [6(OH)-DA]-lesioned rat. This effect was mimicked by (-)-nicotine (0.35 mg/kg s.c.). Both (+/-)-epibatidine- and (-)-nicotine-induced turning were significantly inhibited by mecamylamine (3 mg/kg s.c.), indicating that the turning response was mediated by nAChRs. (+/-)-Epibatidine also increased locomotor activity in a dose-dependent manner. (+/-)-Epibatidine-induced hyperactivity was blocked by D1 and D2 receptor antagonists, SCH 23390 and eticlopride, respectively, suggesting that both dopamine receptor subtypes might be required for the locomotor effect of (+/-)-epibatidine. These results demonstrate that (+/-)-epibatidine displays nAChR agonist activity in the rat CNS and that certain effects are mediated via nAChR-stimulated catecholamine release and subsequent activation of corresponding receptors.