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Effects of ion gradients on the release of neurotransmitter from autonomic nerve endings in vivo.

离子梯度对体内自主神经末梢释放神经递质的影响。

基本信息

批准号：
11670056
负责人：
YAMAZAKI Toji
金额：
$ 0.64万
依托单位：
National Cardiovascular Center, Research Institute
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

1) To investigate the effect of hypoxia on endogenous norepinephrine (NE) release from cardiac sympathetic nerve ending, we administered sodium cyanide (NaCN) for 30 min into the myocardial interstitial space through a dialysis probe and measured dialysate NE levels. During the NaCN perfusion, a marked and concentration-dependent increase in dialysate NE was observed. This cyanide induced NE response was suppressed by pretreatment with despiramine (a membranous NE transport inhibitor). Further, the cyanide induced NE response was suppressed by pretreatment with TMB-8 (intracellular Ca^<2+> antagonist) but unaffected by ω-conotoxin GVIA (NE releasing inhibitor). Our data suggest that two independent (desipramine or TMB-8 suppressive) mechanisms contributed to the amount of NE efflux induced by cyanide in in vivo cardiac sympathetic nerve.2) Acute myocardial ischemia induced by coronary occlusion increased myocardial interstitial acetylcholine (ACh) and NE levels in ischemic region, whereas, in non-ischemic region, coronary occlusion increased myocardial ACh level but decreased the NE level. The ACh release in the ischemic region is mainly attributed to local release mechanism, whereas the ACh release in the non-ischemic region depends on the increased vagal efferent nerve activity. The local release mechanism would depend on intracellular Ca^<2+> mobilization but not on N-type Ca^<2+> channel opening.

1)为探讨缺氧对心脏交感神经末梢内源性去甲肾上腺素（NE）释放的影响，我们通过透析探头将氰化钠（NaCN）注入心肌间质30 min，并测量透析液NE水平。在NaCN灌注期间，观察到透析液NE显著且浓度依赖性增加。这种氰化物诱导的NE反应被地匹胺（一种膜NE转运抑制剂）预处理抑制。此外，用TMB-8（胞内Ca^2+拮抗剂）预处理可抑制氰化物诱导的NE反应，但不受ω-芋螺毒素GVIA（NE释放抑制剂）的影响。结果表明，地昔帕明或TMB-8抑制剂是氰化物诱导的在体心交感神经NE外排的两种独立机制。2）冠脉结扎引起的急性心肌缺血可增加缺血区心肌间质中的乙酰胆碱（ACh）和NE水平，而在非缺血区，冠脉结扎可增加心肌间质中的ACh水平，但降低NE水平。缺血区的ACh释放主要是局部释放机制，而非缺血区的ACh释放则依赖于迷走神经传出神经活动的增加。局部释放机制可能依赖于细胞内Ca^<2+>动员，而不依赖于N型Ca^<2+>通道开放。