Tuberoinfundibular peptide of 39 residues (TIP39): molecular structure and activity for parathyroid hormone 2 receptor
Tuberoinfundibular peptide of 39 residues (TIP39): molecular structure and activity for parathyroid hormone 2 receptor
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DOI：
10.1016/s0028-3908(02)00335-0
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发表时间：
2003-01-01
影响因子：
4.7
通讯作者：
Wang, H
中科院分区：
文献类型：
--
作者：
Della Penna, K;Kinose, F;Wang, H
最近，基于肽激活甲状旁腺激素2受体（PTH 2 R）的能力，从牛下丘脑纯化了神经肽TIP 39（Usdin等人，Nat. Neurosci. 2（1999）941）。PTH 2 R在神经系统中大量表达，其表达模式提示其可能在垂体功能调节和伤害感受中起作用。为了了解TIP 39和PTH 2 R的生理作用，我们克隆了人、小鼠和大鼠的TIP 39基因。我们的研究结果显示：（1）成熟肽由前体加工而成;（2）TIP 39肽在物种间高度保守;和（3）来自所有物种的TIP 39激活腺苷酸环化酶并通过PTH 2 R提高细胞内钙水平。我们还定义并比较了TIP 39对腺苷酸环化酶激活和通过PTH 2 R的钙动员途径的构效关系，发现了这些途径所需的TIP 39的共同和差异决定簇。此外，我们观察到，TIP 39提高了初级背根神经节神经元的细胞内钙水平，而对PTH 2 R无活性的肽则没有，这表明TIP 39可能通过PTH 2 R依赖性机制激活这些对体内伤害感受重要的神经元。(C)2002爱思唯尔科技有限公司。保留所有权利。
The neuropeptide TIP39 was recently purified from bovine hypothalamus based on the ability of the peptide to activate the parathyroid hormone 2 receptor (PTH2R) (Usdin et al. Nat. Neurosci. 2 (1999) 941). PTH2R is abundantly expressed in the nervous system, and its expression pattern suggests that it may play a role in modulation of pituitary function and in nociception. Towards understanding the physiological role of TIP39 and PTH2R, we cloned human, mouse and rat TIP39 gene. Our results revealed that: (1) the mature peptide is processed from a precursor; (2) TIP39 peptide is highly conserved among species; and (3) TIP39 from all species activates adenylyl cyclase and elevates intracellular calcium levels through PTH2R. We also defined and compared the structure-activity relationship of TIP39 on both activation of adenylyl cyclase and calcium mobilization pathways through PTH2R, finding common and differential determinants of TIP39 that are required for these pathways. Furthermore, we observed that TIP39 elevates intracellular calcium levels in primary dorsal root ganglion neurons whereas the peptide inactive on PTH2R do not, suggesting that TIP39 may activate these neurons important for nociception in vivo through PTH2R-dependent mechanisms. (C) 2002 Elsevier Science Ltd. All rights reserved.