Evidence for a common evolutionary origin of brain and pancreas cholecystokinin receptors.
Evidence for a common evolutionary origin of brain and pancreas cholecystokinin receptors.
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大脑和胰腺胆囊收缩素受体共同进化起源的证据。
DOI：
10.1073/pnas.83.12.4355
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发表时间：
1986
影响因子：
11.1
通讯作者：
Williams,JA
中科院分区：
文献类型：
--
作者：
Vigna,SR;Thorndyke,MC;Williams,JA
研究了哺乳动物脑和胰腺中胆囊收缩素（CCK）受体不同形式的进化基础。鼠鱼、青蛙、蛇和鸡的大脑和胰腺含有可饱和的、高亲和力的碘化猪CCK-33结合位点。在变温动物中，脑和胰腺CCK受体对各种CCK和胃泌素表现出几乎相同的相对特异性。硫酸化CCK-8和硫酸化胃泌素-17是最有效的，而它们的非硫酸化类似物和胃泌素-4效力较低。相比之下，在鸡中，大脑和胰腺CCK受体的特异性与哺乳动物受体非常相似。我们的结论是，大脑和胰腺CCK受体结合CCK和胃泌素的新的特异性进化的水平上的分歧的恒温动物（鸟类和哺乳动物）从爬行动物。我们认为，先前的进化胃泌素提供了这些变化的选择压力。吸热胰腺受体在进化中通过将其对硫酸化酪氨酸残基在其配体中的位置的要求从羧基末端的第六或第七位置缩小到仅第七位置而出现。在进化过程中，内皮脑受体失去了对硫酸化配体的需求，并将其高亲和力结合结构域从CCK和胃泌素羧基末端的酪氨酸残基转移到CCK和胃泌素共同的羧基末端四肽活性位点。
An evolutionary basis for the distinct forms of cholecystokinin (CCK) receptors in the mammalian brain and pancreas was examined. The brains and pancreases of ratfish, frog, snake, and chicken contained saturable, high-affinity binding sites for iodinated porcine CCK-33. In the ectothermic species, the brain and pancreas CCK receptors exhibited nearly the same relative specificities for various CCKs and gastrins. Sulfated CCK-8 and sulfated gastrin-17 were the most potent while their nonsulfated analogs and gastrin-4 were less potent. By contrast, in the chicken, the specificities of brain and pancreas CCK receptors closely resembled their mammalian counterparts. We conclude that brain and pancreas CCK receptors with new specificities for binding CCKs and gastrins evolved at the level of the divergence of endotherms (birds and mammals) from reptiles. We propose that the prior evolution of gastrin provided the selection pressure for these changes. The endotherm pancreas receptor arose in evolution by narrowing its requirement for the position of a sulfated tyrosine residue in its ligands from either the sixth or seventh position from the carboxyl terminus to the seventh position only. The endotherm brain receptor arose in evolution by losing its requirement for a sulfated ligand and by transferring its high-affinity binding domain from the tyrosine residue in the carboxyl termini of CCK and gastrin to the carboxyl-terminal tetrapeptide active site common to CCKs and gastrins.