C型利钠肽及其受体的结构和功能

Constructions and functions of C-type natriuretic peptide and its receptor

C型利钠肽（c-type natriuretic peptide,CNP）是利钠肽家族的一员,分子结构中也有一个由二硫键连接而成的含17个氨基酸的环状结构,CNP基因至少有两个外显子编码前CNP原,体内成熟的CNP以22和53肽的形式存在。CNP选择作用于受体NPR-B（natriuretic peptide receptorB）,也与心钠素、脑钠素一样作用于NPR-C（natriuretic pep-tide clearance receptor）。NPR-B为一次跨膜受体,其C末端有鸟甘酸环化酶活性,通过催化cGMP的产生来介导CNP的作用。CNP的合成和释放受多种细胞因子的调节,通过与NPR-C结合而内吞或直接被中性内肽酶水解两条途径降解。CNP及其受体广泛分布于血管、血液、中枢神经系统等组织细胞,起扩张血管、抗焦虑、调节细胞生长及内分泌等作用。

C-type natriuretic peptide (CNP) shows remarkable sequence homology to atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) within the 17-residue ring portion formed by a pair of cysteine residues and being the third member of the natriuretic peptide family. Sequence analysis reveals that there are at least two exons in the coding region for preproCNP. Mature forms of CNP in body are CNP22 and its N-termi-nally elongated form CNP53. As an agonist, CNP selectively bind to natriuretic peptide receptor B (NPR-B) which has a single member-spanning helical domain and exert its biological effects by activating its C-teminal guanylate cyclase to catalyse formation of cyclic guanosine monophosphate (cGMP). CNP can also bind to natriuretic peptidereceptor C (NPR-C) which has high binding affinities for all of the natriuretic peptides. The synthesis and release of CNP are regulated by many cy-tokines, and CNP is metabolized by two main pathways : internalization and degradation through the binding with NPR-C or hydrolysis by neutral endopeptidase. CNP and its receptor distribute widespreadly in various tissues including vessels, blood and central neural systems, and produce effects of vasodilation, antianxiely effect and regulations of cell proliferation and endocrine.