Insecticides affecting acetylcholine receptor interactions.
Insecticides affecting acetylcholine receptor interactions.
复制标题
影响乙酰胆碱受体相互作用的杀虫剂。
DOI：
10.1016/0163-7258(82)90031-6
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发表时间：
1982
影响因子：
13.5
通讯作者：
Eldefrawi,ME
中科院分区：
文献类型：
--
作者：
Eldefrawi,AT;Mansour,NA;Eldefrawi,ME
受体可以定义为具有高度选择性和立体特异性的分子，它们携带化学信使的识别位点。它们通常是细胞膜的组成部分，迄今为止发现的大多数受体都是蛋白质。术语“神经递质受体”描述的是携带神经递质识别位点的分子，如乙酰胆碱（ACh）或去甲肾上腺素，这些神经递质通常但不限于存在于神经元、神经肌肉和神经腺突触（突触是两个细胞之间的功能性接触点）。正常情况下，神经刺激导致神经递质从神经末梢释放到突触间隙，扩散到突触后膜，在那里它与受体发生反应并引发细胞反应。通过再摄取机制（在肾上腺素能突触中）或酶解机制（在胆碱能突触中）从受体附近的化学物质移除，神经递质的作用很快终止，此外还有一些扩散损失。直到十年前，我们对神经递质受体的了解还只是它们一定存在。最近流行的观点是功能性受体只存在于完整的细胞中，但是Sutherland和合作者（Robison et al., 1977,1971）通过证明对激素的反应可以在亚细胞制剂中测量，证明了事实并非如此。在这一突破之后，引入了使用高比活性放射性标记配体来识别亚细胞制剂中的受体的结合试验，为体外鉴定和纯化神经递质受体铺平了道路。通过生物物理手段对骨骼肌神经肌肉连接处的ach受体功能进行了广泛的研究，但生物化学研究大多是在鱼的电器官中发现的类似受体。18世纪，法拉第首先在这些器官中发现了电（Dubois-Raymond, 1887）。电鳗（Electrophorus electricus）和鳐（Torpedo sp.）的电器官都是胚胎时期由骨骼肌发育而来的。它们被胆碱能运动神经元激活，像骨骼肌一样具有化学兴奋性（凯恩斯和马丁斯-费雷拉，1953）。作为对神经刺激的反应，电器官细胞（electroplax）产生电位而不是收缩。这些组织的可获得性、ach受体的丰富性以及对其生理学和药理学知识的积累是电器官ach受体是第一个以纯形式分离出来的ach受体的原因。
Receptors may be defined as highly selective and stereospecific molecules that carry recognition sites for chemical messengers. They are normally constituents of cell membranes, and most receptors identified to date are proteins. The term neurotransmitter receptor describes the molecule carrying recognition sites for neurotransmitters such as acetylcholine (ACh) or norepinephrine, which are usually but not exclusively found at neuronal, neuromuscular and neuroglandular synapses (synapses being functional contact points between two cells). Normally, neuronal stimulation results in release of the neurotransmitter from the nerve endings into the synaptic gap, which diffuses to the postsynaptic membrane where it reacts with the receptor and triggers a cellular response. The action of the neurotransmitter is terminated quickly by removal of the chemical from the vicinity of the receptor, either by a reuptake mechanism (in adrenergic synapses), or by enzymatic hydrolysis (in cholinergic synapses), in addition to some loss by diffusion.Until a decade ago all we knew about neutransmitter receptors was that they must exist. The prevailing notion of the recent past was that functional receptors are found only in intact cells, but Sutherland and collaborators (Robison et al., 1970, 1971) proved otherwise by demonstrating that response to hormones may be measured in subcellular preparations. Following that breakthrough, the introduction of binding assays using high specific activity radiolabeled ligands to identify receptors in subcellular preparations paved the way for the in vitro identification and purification of neurotransmitter receptors. ACh-receptor function has been studied extensively by biophysical means at the neuromuscular junction of skeletal muscle, but biochemical studies have been mostly of a similar receptor found in fish electric organs. Electricity was first discovered in these organs by Faraday in the 18th century (Dubois-Raymond, 1887). The electric organs of the electric eel, Electrophorus electricus, and the ray, Torpedo sp., are derived embryonically from skeletal muscles. They are activated by cholinergic motor neurons and are chemically excitable like skeletal muscles (Keynes and Martins-Ferreira, 1953). In response to nerve stimulation the electric organ cell (electroplax) generates electric potentials instead of contraction. The availability of these tissues, their richness in AChreceptors and the accumulated knowledge on their physiology and pharmacology are the reasons that ACh-receptors of electric organs were the first ACh-receptors to be isolated in pure form.