Mitchelson Frederick
Department of Pharmacology, University of Melbourne, Melbourne, VIC 3010, Australia.
Handb Exp Pharmacol. 2012(208):263-98. doi: 10.1007/978-3-642-23274-9_12.
Muscarinic agonists act mainly via muscarinic M₃ cholinoceptors to cause contraction of the iris sphincter, ciliary muscle and trabecular meshwork as well as increase outflow facility of aqueous humour. In the iris dilator, the effect of muscarinic agonists is species dependent but is predominantly relaxation via muscarinic M₃ receptors. In the conjunctiva, muscarinic agonists stimulate goblet cell secretion which contributes to the protective tear film. Muscarinic M₂ and M₃ receptors appear mainly involved. In the lens muscarinic agonists act via muscarinic M₁ receptors to produce depolarization and increase Ca(2+). All five subtypes of muscarinic receptor are present in the retina. In the developing retina, acetylcholine appears to limit purinergic stimulation of retinal development and decrease cell proliferation. In the adult retina acetylcholine and other muscarinic agonists may have complex effects, for example, enhancing light-evoked neuronal firing in transient ON retinal ganglion cells and inhibiting firing in OFF retinal ganglion cells. In the lacrimal gland, muscarinic agonists activate M₃ receptors on secretory globular acinar cells to stimulate tear secretion and also cause contraction of myoepithelial cells. In Sjögren's syndrome, antibodies to the muscarinic M₃ receptor disrupt normal gland function leading to xerophthalmia although the mechanism of action of the antibody is still not clear. Atropine and pirenzepine are useful in limiting the development of myopia in children probably by an action on muscarinic receptors in the sclera, although many other muscarinic receptor antagonists are not effective.
毒蕈碱激动剂主要通过毒蕈碱M₃胆碱能受体发挥作用，引起虹膜括约肌、睫状肌和小梁网收缩，并增加房水流出率。在虹膜开大肌中，毒蕈碱激动剂的作用因物种而异，但主要是通过毒蕈碱M₃受体产生松弛作用。在结膜中，毒蕈碱激动剂刺激杯状细胞分泌，这有助于形成保护性泪膜。毒蕈碱M₂和M₃受体似乎主要参与其中。在晶状体中，毒蕈碱激动剂通过毒蕈碱M₁受体发挥作用，产生去极化并增加细胞内钙离子浓度。视网膜中存在所有五种毒蕈碱受体亚型。在发育中的视网膜中，乙酰胆碱似乎限制嘌呤能对视网膜发育的刺激并减少细胞增殖。在成年视网膜中，乙酰胆碱和其他毒蕈碱激动剂可能具有复杂的作用，例如，增强瞬态ON视网膜神经节细胞的光诱发神经元放电并抑制OFF视网膜神经节细胞的放电。在泪腺中，毒蕈碱激动剂激活分泌性球状腺泡细胞上的M₃受体以刺激泪液分泌，并还引起肌上皮细胞收缩。在干燥综合征中，毒蕈碱M₃受体抗体破坏正常腺体功能，导致干眼症，尽管该抗体的作用机制仍不清楚。阿托品和哌仑西平可能通过作用于巩膜中的毒蕈碱受体来限制儿童近视的发展，尽管许多其他毒蕈碱受体拮抗剂无效。
