Neurochemical correlates of opiate receptor regulation.
Neurochemical correlates of opiate receptor regulation.
复制标题
阿片受体调节的神经化学相关性。
DOI：
10.1016/0006-2952(86)90314-x
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发表时间：
1986
影响因子：
5.8
通讯作者：
Tempel,A
中科院分区：
文献类型：
--
作者：
Zukin,RS;Tempel,A
阿片剂和阿片肽对神经组织的作用是由p、6、k和o受体介导的[综述见参考文献。L-31。P受体是吗啡类阿片类药物产生镇痛和其他各种经典阿片效应的高亲和力部位。6受体对自然产生的脑啡肽(一类较短的阿片肽)的亲和力高于对吗啡的亲和力。K受体是酮环氮唑类阿片类药物产生止痛以及它们独特的共济失调和镇静作用的部位。最近，它被定义为强啡肽(一种17个氨基酸的阿片肽)的高度选择性受体。α受体介导SKF-10,047(N-烯丙基去甲环唑)和其他阿片类药物的拟精神和兴奋作用。这些受体表现出相当不同的配体选择性模式，广泛分布于中枢神经系统，并表现出不同的神经解剖学分布[4-81]。研究表明，在神经细胞系中，阿片类药物诱导的腺苷环化酶抑制[9,101]，在脑和细胞系中，鸟苷对激动剂结合的调节作用[11-141]，使得p和6受体可能通过抑制性鸟苷结合蛋白(Ni)与环化酶偶联。现已证实，p、6和K受体由三类阿片肽组成，即脑啡肽、脑啡肽和强啡肽。然而，目前尚不清楚这些受体代表的是不同的基因产物，还是翻译后修饰的单一基因产物。此外，出现的问题是，它们是以协调的方式还是以独立的方式进行管理。阿片类镇痛剂在体内产生耐受和依赖，在体外产生脱敏作用。对这些现象的观察提出了一个问题，即阿片受体在体内是否会因长期服用阿片类药物而上调或下调。阿片受体下调一直很难被记录下来。几个小组报告说，在体内长期服用麻醉性激动剂不会在受体数量或亲和力方面产生任何变化[15-211]。另一方面，在神经肿瘤细胞中观察到受体下调。
The actions of opiates and opioid peptides upon nervous tissue are mediated by p, 6, K, and oreceptors [for reviews see Refs. l-31. The p receptor is the high affinity site at which morphine-like opiates produce analgesia and a variety of other classical opiate effects. The 6 receptor exhibits a higher affinity for the naturally occurring enkephalins (a class of shorter opioid peptides) than for morphine. The K receptor is that site at which ketocyclazocine-like opiates produce analgesia, as well as their unique ataxic and sedative effects. More recently, it has been defined as a receptor highly selective for dynorphin (a 17 amino acid opioid peptide). The areceptor mediates the psychotomimetic and stimulant effects of SKF-10,047 (N-allylnorcyclazocine) and other o opiates. These receptors exhibit rather different ligand selectivity patterns, are widely distributed in the central nervous system, and exhibit diverse neuroanatomical distributions [4-81. Findings from studies in neuronal cell lines demonstrating opiateinduced inhibition of adenylate cyclase [9, 101 and in brain and cell lines showing guanyl nucleotide modulation of agonist binding [ll-141 make it likely that the p and 6 receptors are coupled to cyclase through an inhibitory guanyl nucleotide binding protein (Ni). It is now well-established that the p, 6, and K receptors are subserved by three classes of opioid peptides, pendorphin, the enkephalins, and dynorphin-related peptides. It is, however, unknown whether these receptors represent different gene products or a single gene product which has been post-translationally modified. Moreover, the question arises as to whether they are regulated in a coordinated or an independent manner. Opiate analgesics are well-known to produce tolerance and dependence in vivo and desensitization in vitro. The observation of these phenomena has raised the question as to whether opiate receptors undergo up-or downregulation in vivo, in response to long-term administration of opiate drugs. Opiate receptor downregulation has been difficult to document. Several groups have reported that chronic administration of narcotic agonists in vivo does not produce any change in either receptor number or affinity [15-211. On the other hand, receptor downregulation has been observed in neurotumor cell