Identification of second and third calcitonin receptor-stimulating peptides in porcine brain.

Identification of second and third calcitonin receptor-stimulating peptides in porcine brain.
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DOI:
10.1016/s0006-291x(03)01413-x
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发表时间:
2003-08
影响因子:
3.1
通讯作者:
T. Katafuchi;K. Hamano;K. Kikumoto;N. Minamino
T. Katafuchi;K. Hamano;K. Kikumoto;N. Minamino
中科院分区:
生物学4区
文献类型:
--
作者:
T. Katafuchi;K. Hamano;K. Kikumoto;N. Minamino

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通过与猪下丘脑降钙素受体刺激肽(calcitonin receptor-stimulating peptides,CRSPs)cDNA的交叉杂交,从猪下丘脑cDNA文库中克隆到了两个新的CRSPs,命名为CRSP-2和CRSP-3。CRSP-2和CRSP-3的氨基酸序列与CRSP-1的同源性分别高于降钙素基因相关肽(CGRP)的同源性,这3种CRSP被认为是CGRP超家族中的一个新家族。RT-PCR分析表明CRSP-2和CRSP-3基因转录本主要在中枢神经系统和甲状腺中表达。与CRSP和降钙素(CT)相比,合成的CRSP-2和CRSP-3在LLC-PK 1细胞中非常弱地刺激cAMP产生。此外,CRSP-2和CRSP-3在表达CT受体或CT样受体的COS-7细胞中完全不引起cAMP升高,无论是否有一种受体活性修饰蛋白。这些结果表明CGRP超家族中肽的作用机制和功能仍未确定。
We identified two cDNAs encoding new calcitonin receptor-stimulating peptides (CRSPs) in porcine hypothalamus cDNA library by cross-hybridization with the CRSP cDNA, and designated the second and third peptides as CRSP-2 and CRSP-3. The putative amino acid sequences of prepro-CRSP-2 and prepro-CRSP-3 showed higher identity with that of prepro-CRSP-1 than that of prepro-calcitonin gene-related peptide (CGRP), respectively, and these three CRSPs are considered to form a new family in the CGRP superfamily. RT-PCR analysis demonstrated that both CRSP-2 and CRSP-3 gene transcripts were expressed mainly in the central nervous system and thyroid gland. Synthetic CRSP-2 and CRSP-3 stimulated cAMP production very weakly in LLC-PK1cells compared with CRSP and calcitonin (CT). Furthermore, CRSP-2 and CRSP-3 did not elicit a cAMP elevation at all in the COS-7 cells expressing CT receptor or CT-like receptor with or without one of receptor activity-modifying proteins. These results suggest the presence of still unidentified action mechanisms and functions of the peptides in the CGRP superfamily.