Neuroprotection factor of C-type natriuretic peptide (CNP)

c型利钠肽（CNP）属于利钠肽家族，具有分子内二硫键形成的环状结构，在心房利钠肽（ANP）和脑利钠肽（BNP）与CNP之间保守存在。ANP和BNP主要作为心脏激素从心脏分泌，而CNP主要定位于中枢神经系统（CNS），但CNP在中枢神经系统中的功能迄今尚未明确。利钠肽受体主要有鸟苷酸环化酶a （GC-A）和鸟苷酸环化酶b （GC-B）。ANP和BNP对GC-A具有高亲和力，而CNP优先与GC-B结合。GC-A和GC-B都能引起细胞内cGMP的增加，而cGMP介导了利钠肽的大部分生物作用。神经营养肽垂体腺苷酸环化酶激活多肽（PACAP）在培养的星形胶质细胞中刺激腺苷酸环化酶活性。在利用DNA芯片研究PACAP对星形胶质细胞影响的过程中，我们发现PACAP刺激的星形胶质细胞中CNP基因表达明显增加。然后，我们试图阐明PACAP如何调节星形胶质细胞中CNP的生物合成和分泌。在大鼠培养的星形胶质细胞中，垂体PACAP以剂量和时间依赖的方式激活CNP的基因表达和分泌。这些结果提示PACAP可能参与了星形胶质细胞CNP生物合成的调控。

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family and has a ring structure formed by an intramolecular disulfide bond, which is conserved among atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP),and CNP. ANP and BNP are mainly secreted from heart as cardiac hormones, whereas CNP is mainly localized in the central nervous system (CNS),but the function of CNP in the CNS has not been clarified so far. Receptors for natriuretic peptides are mainly guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B). ANP and BNP show high affinity to GC-A, whereas, CNP preferentially binds to GC-B. Both GC-A and GC-B elicit an increase in intracellular cGMP that mediates most of the biological actions of natriuretic peptides. It has been reported that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP)s timulates adenylate cyclase activity in cultured astrocytes. During the course of a study regarding the effect of PACAP on astrocytes with DNA microarray, we found that CNP gene expression was markedly increased in astrocytes stimulated by PACAP. Then, we tried to clarify how PACAP regulates the biosynthesis and secretion of CNP in the astrocytes. In rat-cultured astrocytes, pituitary PACAP activates gene expression and secretion of CNP in a dose- and time-dependent manner. These results suggest that PACAP might be involved in,the regulation of CNP biosynthesis in astrocytes.