查看Ch14 The Autonomic Nervous System的源代码

=== 所有节后副交感神经元都释放 ACh 并刺激内脏靶标上的毒蕈碱受体 ===
<b style=color:#0ae>All postganglionic parasympathetic neurons release ACh and stimulate muscarinic receptors on visceral targets</b>

All postganglionic parasympathetic neurons act through muscarinic ACh receptors on the postsynaptic target (see Fig. 14-8). Activation of this receptor can either stimulate or inhibit function of the target cell. Cellular responses induced by muscarinic receptor stimulation are more varied than are those induced by nicotinic receptors. Muscarinic receptors are G protein–coupled receptors (GPCRs; see pp. 51–66)— also known as metabotropic receptors—that (1) stimulate the hydrolysis of phosphoinositide and thus increase [Ca2+]i and activate protein kinase C, (2) inhibit adenylyl cyclase and thus decrease cAMP levels, or (3) directly modulate K+ channels through the G-protein βγ complex (see pp. 197–198 and 542). Because they are mediated by second messengers, muscarinic responses, unlike the rapid responses evoked by nicotine receptors, are slow and prolonged.

所有节后副交感神经元都通过突触后靶标上的毒蕈碱 ACh 受体起作用（见图 14-8）。该受体的激活可以刺激或抑制靶细胞的功能。毒蕈碱受体刺激诱导的细胞反应比烟碱受体诱导的细胞反应更多样化。毒蕈碱受体是 G 蛋白偶联受体 （GPCR;见第 51-66 页）— 也称为代谢受体— （1） 刺激磷酸肌醇的水解，从而增加 [Ca2+]i 并激活蛋白激酶 C，（2） 抑制腺苷酸环化酶，从而降低 cAMP 水平，或 （3） 通过 G 蛋白 βγ 复合物直接调节 K+ 通道（参见第 197-198 页和第 542 页）。因为它们是由第二信使介导的，所以毒蕈碱反应与尼古丁受体诱发的快速反应不同，是缓慢而持久的。


Muscarinic receptors exist in five different pharmacological subtypes (M1 to M5) that are encoded by five different genes. All five subtypes are highly homologous to each other but very different from the nicotinic receptors, which are ligand-gated ion channels. Subtypes M1 through M5 are each stimulated by ACh and muscarine and are blocked by atropine. These muscarinic subtypes have a heterogeneous distribution among tissues, and in many cases a given cell may express more than one subtype. N14-3 Although a wide variety of antagonists inhibit the muscarinic receptors, none is completely selective for a specific subtype. However, it is possible to classify a receptor on the basis of its affinity profile for a battery of antagonists. Selective agonists for the different isoforms have not been available.

毒蕈碱受体存在于 5 种不同的药理学亚型 （M1 至 M5） 中，由 5 个不同的基因编码。所有五种亚型彼此高度同源，但与烟碱受体非常不同，烟碱受体是配体门控离子通道。M1 至 M5 亚型分别受到 ACh 和毒蕈碱的刺激，并被阿托品阻断。这些毒蕈碱亚型在组织之间具有异质性分布，在许多情况下，给定的细胞可能表达不止一种亚型。N14-3 尽管多种拮抗剂抑制毒蕈碱受体，但没有一种对特定亚型具有完全选择性。然而，可以根据受体对一组拮抗剂的亲和力特征对受体进行分类。目前还没有针对不同亚型的选择性激动剂。


A molecular characteristic of the muscarinic receptors is that the third cytoplasmic loop (i.e., between the fifth and sixth membrane-spanning segments) is different in M1, M3, and M5 on the one hand and M2 and M4 on the other. This loop appears to play a role in coupling of the receptor to the G protein downstream in the signal-transduction cascade. In general M1, M3, and M5 preferentially couple to Gαq and then to phospholipase C, with release of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (see p. 58). On the other hand M2 and M4 preferentially couple to Gαi or Gαo to inhibit adenylyl cyclase and thus decrease [cAMP]i (see p. 53).

毒蕈碱受体的分子特征是第三个细胞质环（即，在第五和第六跨膜段之间）一方面在 M1、M3 和 M5 上不同，另一方面在 M2 和 M4 上不同。该环似乎在信号转导级联反应中受体与下游 G 蛋白的偶联中发挥作用。通常，M1、M3 和 M5 优先与 Gαq 偶联，然后与磷脂酶 C 偶联，释放肌醇 1,4,5-三磷酸 （IP3） 和甘油二酯（见第 58 页）。另一方面，M2 和 M4 优先与 Gαi 或 Gαo 偶联以抑制腺苷酸环化酶，从而降低 [cAMP]i（见第 53 页）。

<br>