Jerusalinsky D, Kornisiuk E, Alfaro P, Quillfeldt J, Ferreira A, Rial V E, Durán R, Cerveñansky C
Instituto de Biología Celular y Neurociencias Profesor Eduardo De Robertis, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
Toxicon. 2000 Jun;38(6):747-61. doi: 10.1016/s0041-0101(99)00196-8.
Muscarinic receptors are widely spread throughout the body, and are involved in the regulation of fundamental physiological processes, like the modulation of the heart rate, control of motor systems and modulation of learning and memory. In the central nervous system the cholinergic transmission is mainly mediated by muscarinic receptors; there are five subtypes that are all expressed in the brain of mammals (m1-m5). There are regional differences in their concentrations in the brain and more than one subtype is expressed in the same cell. It has been difficult to study their localization and function in vivo due to the lack of ligands that exclusively act on one subtype of the receptor. We studied the action of the muscarinic toxins MT1, MT2 and MT3, from the venom of the snake Dendroaspis angusticeps, on muscarinic receptors, by using the classical muscarinic radioligand 3H-NMS as reporter of the inhibition of its own binding, to either native or cloned receptors. We have also studied the in vivo effects on memory retention of the injection of the toxins into discrete brain regions. The muscarinic toxins appear to be invaluable tools to study receptor pharmacology, physiology and structure/function relationships. They would enable the design of new, more selective, pharmacological agents.
毒蕈碱受体广泛分布于全身，参与调节基本生理过程，如心率调节、运动系统控制以及学习和记忆调节。在中枢神经系统中，胆碱能传递主要由毒蕈碱受体介导；存在五种亚型，均在哺乳动物大脑中表达（m1 - m5）。它们在大脑中的浓度存在区域差异，且同一细胞中可表达不止一种亚型。由于缺乏专门作用于一种受体亚型的配体，在体内研究它们的定位和功能一直很困难。我们通过使用经典的毒蕈碱放射性配体3H - NMS作为其自身结合抑制的报告物，来研究来自绿曼巴蛇毒液的毒蕈碱毒素MT1、MT2和MT3对天然或克隆受体的作用。我们还研究了将毒素注射到离散脑区对记忆保持的体内影响。毒蕈碱毒素似乎是研究受体药理学、生理学和结构/功能关系的宝贵工具。它们将有助于设计新的、更具选择性的药物制剂。
