查看Ch14 The Autonomic Nervous System的源代码

=== 两种最不常见的非经典神经递质 ATP 和一氧化氮首先在 ANS 中被发现 ===
<b style=color:#0ae>Two of the most unusual nonclassic neurotransmitters, ATP and nitric oxide, were first identified in the ANS</b>

It was not until the 1970s that a nonadrenergic, noncholinergic class of sympathetic or parasympathetic neurons was first proposed by Geoffrey Burnstock and colleagues, who suggested that ATP might act as the neurotransmitter. This idea, that a molecule used as an intracellular energy substrate could also be a synaptic transmitter, was initially difficult to prove. However, it is now clear that neurons use a variety of classes of molecules for intercellular communication (see pp. 314–322). Two of the most surprising examples of nonclassic transmitters, nitric oxide (NO) and ATP, were first identified and studied as neurotransmitters in the ANS, but they are now known to be more widely used throughout the nervous system.

直到 1970 年代，Geoffrey Burnstock 及其同事才首次提出了一类非肾上腺素能、非胆碱能的交感神经或副交感神经神经元，他们认为 ATP 可能充当神经递质。这个想法，即用作细胞内能量基质的分子也可以是突触递质，最初很难证明。然而，现在很明显，神经元使用各种类别的分子进行细胞间通讯（参见第 314-322 页）。非经典递质的两个最令人惊讶的例子，一氧化氮 （NO） 和 ATP，首先在 ANS 中被确定和研究为神经递质，但现在已知它们在整个神经系统中得到更广泛的应用。


<b style=color:#f80>ATP</b> ATP is colocalized with norepinephrine in postganglionic sympathetic vasoconstrictor neurons. It is contained in synaptic vesicles, is released on electrical stimulation, and induces vascular constriction when it is applied directly to vascular smooth muscle. The effect of ATP results from activation of P2 purinoceptors on smooth muscle, which include ligand-gated ion channels (P2X) and GPCRs (P2Y and P2U). P2X receptors are present on autonomic neurons and smooth-muscle cells of blood vessels, the urinary bladder, and other visceral targets. P2X receptor channels have a relatively high Ca2+ permeability (see p. 327). In smooth muscle, ATP-induced depolarization can also activate voltage-gated Ca2+ channels (see pp. 189–190) and thus lead to an elevation in [Ca2+]i and a rapid phase of contraction (Fig. 14-10).

<b style=color:#f80>ATP</b> ATP 与去甲肾上腺素共定位于节后交感神经血管收缩神经元中。它包含在突触囊泡中，在电刺激下释放，当它直接应用于血管平滑肌时会诱导血管收缩。ATP 的影响是由于 P2 嘌呤受体对平滑肌的激活而产生的，平滑肌包括配体门控离子通道 （P2X） 和 GPCR （P2Y 和 P2U）。P2X 受体存在于自主神经元和血管、膀胱和其他内脏靶标的平滑肌细胞上。P2X 受体通道具有相对较高的 Ca2+ 通透性（参见第 327 页）。在平滑肌中，ATP 诱导的去极化还可以激活电压门控的 Ca2+ 通道（参见第 189-190 页），从而导致 [Ca2+]i 升高和快速收缩阶段（图 14-10）。


Norepinephrine, by binding to α1 adrenergic receptors, acts through a heterotrimeric G protein (see pp. 51–66) to facilitate the release of Ca2+ from intracellular stores and thereby produce a slower phase of contraction. Finally, the release of neuropeptide Y may, after prolonged and intense stimulation, elicit a third component of contraction.

去甲肾上腺素通过与 α1 肾上腺素能受体结合，通过异源三聚体 G 蛋白起作用（参见第 51-66 页），以促进 Ca2+ 从细胞内储存中释放，从而产生较慢的收缩阶段。最后，神经肽 Y 的释放，经过长时间和强烈的刺激，可能会引发收缩的第三个组成部分。

<b style=color:#f80>Nitric Oxide</b> In the 1970s, it was also discovered that the vascular endothelium produces a substance that induces relaxation of vascular smooth muscle. First called endothelium-derived relaxation factor, it was identified as the free radical NO in 1987. NO is an unusual molecule for intercellular communication because it is a short-lived gas. It is produced locally from L-arginine by the enzyme nitric oxide synthase (NOS; see pp. 66–67). The NO then diffuses a short distance to a neighboring cell, where its effects are primarily mediated by the activation of guanylyl cyclase. NOS is found in the preganglionic and postganglionic neurons of both the sympathetic and parasympathetic divisions as well as in vascular endothelial cells. It is not specific for any type of neuron inasmuch as it is found in both norepinephrine- and ACh-containing cells as well as neurons containing a variety of neuropeptides. Figure 14-11 shows how a parasympathetic neuron may simultaneously release NO, ACh, and vasoactive intestinal peptide, each acting in concert to lower [Ca2+]i and relax vascular smooth muscle.

<b style=color:#f80>NO</b> 在 1970 年代，还发现血管内皮产生一种诱导血管平滑肌松弛的物质。它最初被称为内皮衍生的松弛因子，于 1987 年被确定为自由基 NO。NO 是一种不常见的细胞间通讯分子，因为它是一种短寿命气体。它是通过一氧化氮合酶 （NOS;见第 66-67 页） 从 L-精氨酸局部产生的。然后，NO 会扩散到邻近细胞，在那里其作用主要由鸟苷酸环化酶的激活介导。NOS 存在于交感神经和副交感神经分支的节前和节后神经元以及血管内皮细胞中。它对任何类型的神经元都没有特异性，因为它存在于含有去甲肾上腺素和 ACh 的细胞以及含有多种神经肽的神经元中。图 14-11 显示了副交感神经元如何同时释放 NO、ACh 和血管活性肠肽，每一种都协同作用以降低 [Ca2+]i 并放松血管平滑肌。

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