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交感后神经纤维(除供应汗腺的神经纤维)释放去甲肾上腺素或正肾上腺素的神经元被称为去甲肾上腺素能或肾上腺素能神经元。去甲肾上腺素、多巴胺、肾上腺素或肾上腺素(又称为表肾上腺素)共同被称为"儿茶酚胺",因为它们含有儿茶酚基团和胺侧链。神经递质释放的五个阶段涉及其合成、储存、释放、重新摄取和代谢。
合成:儿茶酚胺的合成需要酪氨酸,通过载体介导的转运将酪氨酸带到神经细胞质内。酪胺酸羟化酶催化限速步骤,将酪氨酸转化为3,4-二羟基苯丙氨酸(DOPA),该反应受甲酪氨酸的抑制。然后,DOPA经脱羧反应生成多巴胺。多巴胺β-羟化酶将多巴胺转化为去甲肾上腺素,然后储存在突触小泡中。像铜螯合剂和二硫化物一样的药物抑制多巴胺β-羟化酶。此外,苯乙醇胺-甲基转移酶使去甲肾上腺素转化为肾上腺素。
储存:合成的去甲肾上腺素和肾上腺素通过囊泡单胺转运蛋白(VMAT)储存在神经末梢和肾上腺髓质中的囊泡中。
释放:神经冲动的到达和随后的钙离子内流,导致包含去甲肾上腺素的囊泡破裂并将其释放到突触间隙中。释放的去甲肾上腺素与并激活肾上腺素能受体结合,产生所谓的"战斗或逃跑"反应效应。
重新摄取:去甲肾上腺素的作用通过附近细胞的摄取或收缩来终止。大多数神经摄取是通过去甲肾上腺素转运体的帮助来进行的,而细胞外单胺转运蛋白执行细胞外摄取。
代谢和排泄:儿茶酚胺通过儿茶酚-O-甲基转移酶(COMT)和单胺氧化酶(MAO)代谢。MAO将儿茶酚胺转化为醛,进而进一步代谢为羧酸,而COMT将儿茶酚羟基团中的一个甲氧基化为甲氧基衍生物。经过MAO和COMT作用产生的最终产物3-甲氧基-4-羟基苯乙醇(MHPG)在部分缩合之前以葡萄糖醛酸盐或硫酸盐衍生物的形式进行排泄。
节后交感神经纤维中的肾上腺素能神经元释放 NA 作为主要神经递质。
NA 是一种儿茶酚胺,由其代谢前体酪氨酸生物合成衍生,酪氨酸是一种通过钠依赖性载体转运到神经元中的氨基酸。
在细胞质中,酪氨酸被酶促羟基化为 DOPA,DOPA 进一步脱羧为 DA。
通过胺转运蛋白,DA 从细胞质移动到突触囊泡,并经历 β-羟基化以产生 NA。
神经元动作电位的到来触发 Ca2+ 流入神经元细胞质,导致囊泡胞吐作用,在突触间隙释放 NA。
释放的 NA 与神经末梢或效应器官上的受体结合。这会触发细胞级联反应和第二信使的形成,将信号转导为效果。
未使用的 NA 要么扩散到体循环中,要么在突触中被 COMT 灭活,要么经历神经元再摄取。再摄取后,NA 要么被突触囊泡吸收,要么被 毛 氧化。
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