缺陷的AVP不能结合AVPR1A,B并导致神经垂体性尿崩症
中文名称
通路描述
精氨酸加压素 (AVP(20-28)) 是由下丘脑前体蛋白 AVP 切割产生的 9 个氨基酸长的信号肽。它介导肾脏中的水重吸收，其合成和释放受血浆渗透压、血压和/或血容量生理调节。AVP(20-28) 结合位于肾脏集合管基底侧表面的血管加压素受体 AVPR1 和 2。这种结合导致 AVPRs 与 G 蛋白 alpha-s 相互作用。随后发生一系列下游事件，最终导致水通道蛋白 2 (AQP2) 从细胞内储存转运至顶膜表面，作为水重吸收的进入位点。当水平衡达到时，血浆中 AVP(20-28) 水平下降，顶膜 AQP2 水平降低。AVP 的突变使其无法结合肾脏中的 AVPRs，导致水重吸收失调。这可能导致常染色体显性神经垂体性尿崩症 (FNDI)，这是一种以持续多饮 (polydipsia) 和大量尿液排出 (polyuria) 为特征的常染色体显性遗传病，表现为口渴和大量排尿。在 FNDI 中，后叶垂体产生和释放 AVP 的功能受损 (Moeller et al. 2013)。
英文描述
Defective AVP does not bind AVPR1A,B and causes neurohypophyseal diabetes insipidus (NDI) Arginine vasopressin (AVP(20-28)) is a 9 amino-acid long signal peptide produced by cleavage of the precursor protein AVP in the hypothalamus. It mediates the reabsorption of water in the kidney and its synthesis and release are physiologically regulated by plasma osmolarity, blood pressure and/or blood volume. AVP(20-28) binds to vasopressin receptors AVPR1 and 2, located on the basolateral surface of the kidney collecting duct. This binding results in interaction of AVPRs with the G protein alpha-s. Following a cascade of downstream events, ultimately the water channel aquaporin 2 (AQP2) translocates from intracellular stores to the apical surface where it functions as the entry site for water reabsorption. When water balance is achieved, plasma levels of AVP(20-28) drop and AQP2 levels in the apical plasma membrane are decreased.
Mutations in AVP make it unavailable to its AVPRs in the kidney, resulting in dysregulation of water reabsorption. This can cause familial neurohypophyseal diabetes insipidus (FNDI), an autosomal dominant disorder characterised by persistent excessive thirst resulting in constant drinking (polydipsia) and passage of large volumes of urine (polyuria). In FNDI, the production and release of AVP from the posterior pituitary gland is impaired (Moeller et al. 2013).
Mutations in AVP make it unavailable to its AVPRs in the kidney, resulting in dysregulation of water reabsorption. This can cause familial neurohypophyseal diabetes insipidus (FNDI), an autosomal dominant disorder characterised by persistent excessive thirst resulting in constant drinking (polydipsia) and passage of large volumes of urine (polyuria). In FNDI, the production and release of AVP from the posterior pituitary gland is impaired (Moeller et al. 2013).
所含基因
2 个基因