M型胆碱受体

General characteristics and M1 cholinergic receptors

Muscarinic acetylcholine receptors are predominantly located on the postsynaptic membrane of effector organs innervated by postganglionic parasympathetic fiber terminals. There are several main subtypes, differing in localization and elicited effects.

M1 cholinergic receptors are diffusely distributed in cholinergic synapses of the central nervous system (cortex, brainstem, midbrain, and spinal cord), where they are responsible for neuronal transmission.

它们最重要的外周功能是调节胃酸分泌。在胃中，它们位于肠嗜铬样细胞（ECL细胞）上。这些受体与Gq蛋白偶联，受刺激时会导致细胞质钙离子（Ca²⁺）水平升高。这会触发一个级联反应：ECL细胞释放组胺，进而二次刺激胃壁细胞，使其主动分泌盐酸（HCl）。

M2 cholinergic receptors: regulation of cardiac activity

These receptors are traditionally referred to as "cardiac" receptors. Their main function is the inhibition of cardiac activity through specific ionic mechanisms. When M2 receptors are stimulated, potassium channels are activated, leading to an increased efflux of K⁺ ions and membrane hyperpolarization. Simultaneously, the phosphorylation of calcium channels decreases, reducing the influx of Ca²⁺ ions into cardiomyocytes during depolarization.

Effects on cardiac regions:

• Sinoatrial node (SA node): spontaneous diastolic depolarization slows down, automatism decreases, and consequently, heart rate drops (negative chronotropic effect).
• Atria: contractility decreases (negative inotropic effect), the refractory period is shortened, and impulse conduction through the atria is accelerated.
• Atrioventricular node (AV node): conduction slows down and the refractory period is prolonged (negative dromotropic effect).
• Ventricles: contractility drops insignificantly, as parasympathetic innervation in this area is poorly developed.

In addition to the heart, M2 receptors have a presynaptic localization on the membranes of postganglionic parasympathetic fiber terminals. Their excitation triggers a negative feedback mechanism: the release of the neurotransmitter (acetylcholine) into the synaptic cleft is inhibited.

M3 cholinergic receptors: smooth muscle, glands, and blood vessels

Innervated M3 receptors represent the largest group, responsible for classical parasympathetic effects. Their molecular mechanism of action is also associated with Gq proteins: activation of phospholipase C leads to the production of inositol 1,4,5-trisphosphate, release of Ca²⁺ ions from the sarcoplasmic reticulum, and an increase in their cytoplasmic concentration.

Main targets of M3 receptors:

1. Eye: contraction of the sphincter pupillae muscle occurs (leading to pupil constriction — miosis) and of the ciliary muscle (causing accommodation spasm, adjusting the eye for near vision).
2. Smooth muscles of internal organs: tone increases (except for sphincters) and motility of the bronchi, stomach, intestines, biliary tract, uterus, and urinary bladder is enhanced.
3. Exocrine glands: generalized increase in secretion is observed (salivary, lacrimal, bronchial, gastric, sweat, nasopharyngeal, and intestinal glands).

A special subtype is non-innervated M3 cholinergic receptors. They lack synaptic connections with nerve endings, are localized on the endothelial cells of blood vessels, and respond to agonists circulating in the bloodstream. Stimulation of these receptors leads to the synthesis and release of endothelium-derived relaxing factor (NO — nitric oxide). NO diffuses into the smooth muscle cells of the vascular wall, causing them to relax. As a result, vasodilation occurs and blood pressure decreases.

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该主题的其他拓展内容

• Mechanism of phospholipase C activation and the role of inositol 1,4,5-trisphosphate during M3 receptor stimulation.
• Ionic basis of cardiomyocyte hyperpolarization (the role of potassium and calcium channels).
• Presynaptic regulation: detailed mechanism of negative feedback.
• Biochemistry of endothelium-derived relaxing factor (NO) synthesis and its effect on the vascular wall.

“作用于胆碱能突触的药物”章节的其他主题

本资料由 WhiteCoat Pro 讲师根据医学院校教学大纲编写。仅供教育参考。