The molecular basis of neurotransmission at the muscarinic receptor.
The molecular basis of neurotransmission at the muscarinic receptor.
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毒蕈碱受体神经传递的分子基础。
DOI：
10.1016/0006-2952(81)90248-3
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发表时间：
1981
影响因子：
5.8
通讯作者：
El-Fakahany,E
中科院分区：
文献类型：
--
作者：
Richelson,E;El-Fakahany,E
神经递质、荷尔蒙和许多药物通过与它们的受体特异地相互作用而产生影响。在大多数情况下，这些受体是细胞外表面高度专门化的蛋白质。对于激动剂而不是拮抗剂，这些相互作用可能会导致受体分子的构象变化。这些由激动剂引起的受体变化可能通过改变细胞膜的通透性来影响细胞的电特性，最终导致生物反应。受体激活和细胞反应之间的联系是由各种效应器介导的。已经假设受体和效应器在膜的平面内自由扩散，并且两者的耦合发生在激动剂-受体复合体形成之后[L，21。效应器可以是离子通道或酶(如腺苷环化酶)。在它们是通道的情况下，受体介导的通透性变化可以通过两种可能的方式发生：(A)通道效应器直接与受体偶联，由激动剂诱导的受体分子的构象变化导致效应器的构象变化，从而改变其通透性；或(B)受体的激活通过激活导致这种变化的某些细胞内代谢途径间接导致通透性的变化。受体长期暴露于激动剂(过度刺激)可能会导致受体、效应器或受体-效应器耦合的改变。其结果是脱敏，这可能是许多神经递质受体激活的必然结果。不同的受体可以与共同的效应器相互作用，因此当这些受体被激活时，会在细胞内引起相同的变化。此外，相同的受体可以连接到不同细胞类型上的不同效应器，因此，一旦激活，就会引起该细胞类型特有的变化。神经递质的某些受体可能在某些细胞类型上缺乏效应器，在这种情况下，受体将不起作用。
Neurotransmitters, hormones, and many drugs cause their effects by interacting specifically with their receptors. In most cases these receptors are highly specialized proteins on the outside surface of the cell. For agonists but not antagonists these interactions may induce conformational changes in the receptor molecule. These receptor changes induced by agonists may affect the electrical properties of cells by changing the membrane permeability, which ultimately leads to a biological response. The link between receptor activation and cellular response is mediated by various effecters. It has been hypothesized that receptors and effecters freely diffuse in the plane of the membrane and that coupling of the two takes place after the agonist-receptor complex has formed [l, 21. Effecters may be ion channels or enzymes (eg adenylate cyclase). In the case where they are channels, receptor-mediated permeability changes can arise in two possible ways:(a) the channel effector directly couples to the receptor, and conformational changes in the receptor molecule induced by the agonist result in conformational changes in the effector, thereby altering its permeability; or (b) activation of the receptor indirectly leads to the change in permeability by activating some intracellular metabolic pathway that causes the change. Prolonged exposure of receptors to agonist (over-stimulation) may lead to changes in the receptor, the effector, or the receptor-effector coupling. The result is desensitization which is likely a necessary consequence of activation for many neurotransmitter receptors. Different receptors can interact with common effecters and would therefore cause identical changes within the cell when these receptors are activated. In addition, the same receptor could be linked to different effecters on different cell types and, therefore, upon activation cause changes peculiar to the cell type. It is possible that some receptors for a neurotransmitter lack effecters on certain cell types, and in this case the receptors would be nonfunctioning.