Moeller I, Lew R A, Mendelsohn F A, Smith A I, Brennan M E, Tetaz T J, Chai S Y
Howard Florey Institute of Experimental Physiology and Medicine, Parkville, Victoria, Australia.
J Neurochem. 1997 Jun;68(6):2530-7. doi: 10.1046/j.1471-4159.1997.68062530.x.
Angiotensin IV (Val-Tyr-Ile-His-Pro-Phe) has been reported to interact with specific high-affinity receptors to increase memory retrieval, enhance dopamine-induced stereotypy behavior, and induce c-fos expression in several brain nuclei. We have isolated a decapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr-Gln-Arg-Phe) from sheep brain that binds with high affinity to the angiotensin IV receptor. The peptide was isolated using 125I-angiotensin IV binding to bovine adrenal membranes to assay receptor binding activity. This peptide is identical to the amino acid sequence 30-39 of sheep betaA- and betaB-globins and has previously been named LVV-hemorphin-7. Pharmacological studies demonstrated that LVV-hemorphin-7 and angiotensin IV were equipotent in competing for 125I-angiotensin IV binding to sheep cerebellar membranes and displayed full cross-displacement. Using in vitro receptor autoradiography, 125I-LVV-hemorphin-7 binding to sheep brain sections was identical to 125I-angiotensin IV binding in its pattern of distribution and binding specificity. This study reveals the presence of a globin fragment in the sheep brain that exhibits a high affinity for, and displays an identical receptor distribution with, the angiotensin IV receptor. This globin fragment, LVV-hemorphin-7, may therefore represent an endogenous ligand for the angiotensin IV receptor in the CNS.
据报道，血管紧张素IV（缬氨酸-酪氨酸-异亮氨酸-组氨酸-脯氨酸-苯丙氨酸）可与特定的高亲和力受体相互作用，以增强记忆恢复、增强多巴胺诱导的刻板行为，并在多个脑核中诱导c-fos表达。我们从羊脑中分离出一种十肽（亮氨酸-缬氨酸-缬氨酸-酪氨酸-脯氨酸-色氨酸-苏氨酸-谷氨酰胺-精氨酸-苯丙氨酸），它与血管紧张素IV受体具有高亲和力结合。该肽是利用125I-血管紧张素IV与牛肾上腺膜结合来测定受体结合活性而分离得到的。此肽与羊βA-和βB-珠蛋白的氨基酸序列30-39相同，此前已被命名为LVV-血啡肽-7。药理学研究表明，LVV-血啡肽-7和血管紧张素IV在竞争125I-血管紧张素IV与羊小脑膜结合方面具有同等效力，并表现出完全交叉置换。使用体外受体放射自显影技术，125I-LVV-血啡肽-7与羊脑切片的结合在分布模式和结合特异性上与125I-血管紧张素IV的结合相同。这项研究揭示了羊脑中存在一种珠蛋白片段，它对血管紧张素IV受体具有高亲和力，并显示出相同的受体分布。因此，这种珠蛋白片段LVV-血啡肽-7可能代表中枢神经系统中血管紧张素IV受体的内源性配体。
