Distinct α-noradrenergic receptors differentiated by binding and physiological relationships
Distinct α-noradrenergic receptors differentiated by binding and physiological relationships
复制标题
通过结合和生理关系区分不同的 α-去甲肾上腺素能受体
DOI：
10.1016/0024-3205(79)90283-2
复制
发表时间：
1979
期刊：
影响因子：
6.1
通讯作者：
S. Snyder
中科院分区：
文献类型：
--
作者：
D. U'prichard;S. Snyder
在脑和外周组织中，α-去甲肾上腺素激动剂3h -clonidine， 3h -肾上腺素和3h -去甲肾上腺素的标记位点与α-去甲肾上腺素拮抗剂3h - wh -4101(2-（[2', 6'-二甲氧基]-phenoxyethylamino）甲基苯二氧嘧啶标记的位点不同，也不相互转化。一般来说，激动剂对3h -激动剂标记的位点具有更高的亲和力，而拮抗剂更倾向于3h - wb -4101标记的位点，尽管麦角菌和α-拮抗剂酚妥拉明对这两个位点具有相似的亲和力。外周组织中3h -激动剂和3h - wb -4101位点的相对数量各不相同，心脏和输精管中几乎只有3h - wb -4101位点，兔十二指肠中只有3h -激动剂位点，而唾液腺、脾脏和大脑皮层中这两个位点的数量相似。这两个位点似乎是突触后的，因为6-羟多巴胺治疗并没有减少它们的数量。在输精管中，α-激动剂和拮抗剂的心脏和脾脏药理效力与3h - wb -4101位点的亲和力密切相关，而与3h - wb -4101位点的亲和力密切相关，而在兔十二指肠的药理效力与3h - wb -4101位点的亲和力相关，而与3h - wb -4101位点无关。不同的结合位点与不同的生理反应模式的对应表明存在两种不同类型的突触后α-受体。我们建议将WB-4101标记的位点作为α-1受体，3h -可乐定、3h -去甲肾上腺素和3h -肾上腺素标记的位点作为α-2受体。α-2结合位点的药物效力与突触前α-去甲肾上腺素能自受体相似。
In brain and peripheral tissues the α-noradrenergic agonists3H-clonidine,3H-epinephrine and3H-norepinephrine label sites which are distinct from and do not interconvert with those labeled by the α-noradrenergic antagonist3H-WB-4101 (2-([2', 6'-dimethoxy]-phenoxyethylamino) methylbenzodioxane). In general agonists have higher affinity for sites labeled by the3H-agonists while antagonists prefer sites labeled by3H-WB-4101, though ergots and the α-antagonist phentolamine have similar affinities for the two sites. Peripheral tissues vary in relative numbers of3H-agonist and3H-WB-4101 sites with heart and vas deferens having almost exclusively3H-WB-4101 sites, the rabbit duodenum only3H-agonist sites, while salivary gland, spleen and cerebral cortex display similar numbers of both sites. The two sites appear to be postsynaptic since 6-hydroxydopamine treatment does not reduce their numbers. In vas deferens, heart and spleen pharmacological potencies of α-agonists and antagonists correlate closely with affinities for3H-WB-4101 but not3H-clonidine sites, while potencies in rabbit duodenum correlate with affinities for3H-clonidine but not3H-WB-4101 sites. The correspondence of separate binding sites with distinctive patterns of physiological responses indicates the existence of two discrete types of postsynaptic α-receptors. We propose to designate sites labeled by WB-4101 as α-1 receptors and those labeled by3H-clonidine,3H-norepinephrine and3H-epinephrine as α-2 receptors. Drug potencies at α-2 binding sites resemble their affinities for presynaptic α-noradrenergic autoreceptors.