NPR1（Natriuretic Peptide Receptor 1）是一种膜结合受体，属于鸟苷酸环化酶受体家族，主要与心房钠尿肽（ANP）和脑钠尿肽（BNP）结合，参与调节血压、体液平衡和心血管功能。NPR1通过激活鸟苷酸环化酶产生第二信使cGMP，进而激活蛋白激酶G（PKG），导致血管平滑肌松弛、利尿和排钠，从而降低血压。NPR1主要表达在血管内皮、肾脏和肾上腺等组织，是心血管稳态的关键调节因子。NPR1突变可能导致功能丧失或异常，与高血压、心力衰竭和肾脏疾病相关。例如，功能丧失性突变可能减少cGMP生成，导致血管收缩和血压升高，而某些突变可能增加受体活性，引起低血压。NPR1过表达可能增强利尿和血管舒张作用，但过度激活可能导致低血压和电解质紊乱；而表达降低则可能引发高血压和心血管疾病风险增加。NPR1属于NPR家族（包括NPR1、NPR2和NPR3），这些受体均结合钠尿肽，但NPR1和NPR2通过cGMP信号传导，而NPR3主要参与肽的清除。NPR家族共同参与心血管、肾脏和骨骼系统的调节，但各自配体偏好和功能有所不同。NPR1还与代谢和炎症调节有关，其信号通路可能影响胰岛素敏感性和氧化应激反应。研究NPR1有助于开发治疗高血压和心力衰竭的药物，如ANP类似物或NPR1调节剂。

鸟苷酸环化酶，催化从GTP生产的cGMP的，被分类为可溶性和膜的形式（Garbers和洛韦，1994 [搜索PubMed 7982997]）。膜鸟苷酸环化酶，通常被称为鸟苷酸环化酶A到F，可以形成一个家族的细胞表面受体的具有类似地形结构：包含一种蛋白激酶的细胞外配体结合域，单个跨膜结构域和细胞内区域样结构域和环化酶催化域。 GC-A和GC-B作为受体，钠尿肽;他们也被称为心房利钠肽受体A（NPR1）和B型（NPR2; MIM 108961）。也见NPR3（MIM 108962），其编码的蛋白质仅与配体结合跨膜和37个氨基酸的胞质域。 NPR1是一种膜结合的鸟苷酸环化酶是（分别ANP（MIM 108780）和BNP（MIM 600295），）作为受体为心房和脑利尿钠肽。[由OMIM，2009年5月供给]

Natriuretic Peptide Receptor 1 (NPR1) is a membrane-bound receptor belonging to the guanylyl cyclase receptor family, which serves as a critical regulator of cardiovascular homeostasis by binding primarily to atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Upon ligand binding, NPR1 activates its intrinsic guanylyl cyclase activity to generate the second messenger cyclic guanosine monophosphate (cGMP), which subsequently activates protein kinase G (PKG), triggering a cascade that results in vascular smooth muscle relaxation, diuresis, and natriuresis to effectively lower blood pressure. Distinct from its family members NPR2 and NPR3, which share ligand binding capabilities but differ in signaling outcomes—NPR2 also signals via cGMP while NPR3 primarily mediates peptide clearance—NPR1 is predominantly expressed in vascular endothelium, kidney, and adrenal tissues, where it plays a pivotal role in maintaining fluid balance and hemodynamic stability. Genetic variations in NPR1 can lead to loss-of-function or gain-of-function phenotypes; loss-of-function mutations reduce cGMP production, promoting vasoconstriction and hypertension, whereas hyperactive mutations may cause hypotension, and dysregulated expression levels are linked to conditions such as heart failure, renal disease, and electrolyte imbalances. Beyond its canonical cardiovascular roles, NPR1 signaling intersects with metabolic and inflammatory pathways, potentially influencing insulin sensitivity and oxidative stress responses, thereby highlighting its therapeutic potential in the development of novel agents, such as ANP analogs or direct NPR1 modulators, for the treatment of hypertension, heart failure, and related metabolic disorders.

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