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首页> 外文期刊>Life sciences >Muscarinic receptor subtypes mediating central and peripheral antinociception studied with muscarinic receptor knockout mice. A review.
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Muscarinic receptor subtypes mediating central and peripheral antinociception studied with muscarinic receptor knockout mice. A review.

机译：毒蕈碱受体亚型介导中枢和外周镇痛作用与毒蕈碱受体敲除小鼠研究。回顾。

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To gain new insight into the physiological and pathophysiological roles of the muscarinic cholinergic system, we generated mutant mouse strains deficient in each of the five muscarinic acetylcholine receptor subtypes (M(1)-M(5)). In this chapter, we review a set of recent studies dealing with the identification of the muscarinic receptor subtypes mediating muscarinic agonist-dependent analgesic effects by central and peripheral mechanisms. Most of these studies were carried out with mutant mouse strains lacking M(2) or/and M(4) muscarinic receptors. It is well known that administration of centrally active muscarinic agonists induces pronounced analgesic effects. To identify the muscarinic receptors mediating this activity, wild-type and muscarinic receptor mutant mice were injected with the non-subtype-selective muscarinic agonist, oxotremorine (s.c., i.t., and i.c.v.), and analgesic effects were assessed in the tail-flick and hot-plate tests. These studies showed that M(2) receptors play a key role inmediating the analgesic effects of oxotremorine, both at the spinal and supraspinal level. However, studies with M(2)/M(4) receptor double KO mice indicated that M(4) receptors also contribute to this activity.Recent evidence suggests that activation of muscarinic receptors located in the skin can reduce the sensitivity of peripheral nociceptors. Electrophysiological and neurochemical studies with skin preparations from muscarinic receptor mutant mice indicated that muscarine-induced peripheral antinociception is mediated by M(2) receptors. Since acetylcholine is synthesized and released by different cell types of the skin, it is possible that non-neuronally released acetylcholine plays a role in modulating peripheral nociception. Our results highlight the usefulness of muscarinic receptor mutant mice to shed light on the functional roles of acetylcholine released from both neuronal and non-neuronal cells.
机译：为了获得对毒蕈碱胆碱能系统的生理和病理生理作用的新见解，我们生成了五个毒蕈碱乙酰胆碱受体亚型（M（1）-M（5））中的每一种都缺乏的突变小鼠品系。在本章中，我们回顾了一组有关通过中枢和外周机制介导毒蕈碱激动剂依赖性镇痛作用的毒蕈碱受体亚型的鉴定的最新研究。这些研究大多数是与缺少M（2）或/和M（4）毒蕈碱受体的突变小鼠菌株进行的。众所周知，施用中枢活性毒蕈碱激动剂可引起明显的镇痛作用。为了鉴定介导该活性的毒蕈碱受体，向野生型和毒蕈碱受体突变小鼠注射了非亚型选择性毒蕈碱激动剂，oxotremorine（sc，it和icv），并通过甩尾和镇痛评估了镇痛作用。热板测试。这些研究表明，M（2）受体在介导oxotremorine的镇痛作用中发挥关键作用，无论是在脊髓水平还是在脊髓上水平。但是，对M（2）/ M（4）受体双KO小鼠的研究表明，M（4）受体也有助于这种活性。最近的证据表明，位于皮肤中的毒蕈碱受体的激活可以降低周围伤害感受器的敏感性。电生理和神经化学研究与毒蕈碱受体突变小鼠的皮肤制备表明，毒蕈碱诱导的外周镇痛作用是由M（2）受体介导的。由于乙酰胆碱是由皮肤的不同细胞类型合成和释放的，因此非神经元释放的乙酰胆碱可能在调节外周伤害感受中发挥作用。我们的结果凸显了毒蕈碱受体突变小鼠对揭示神经元和非神经元细胞释放的乙酰胆碱的功能作用的有用性。

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