Ichiki Tomoko, Jinno Atsushi, Tsuji Yoshihisa
Department of General Medicine, Sapporo Medical University, S1 W17, Sapporo 060-8556, Japan.
Biology (Basel). 2022 Jun 3;11(6):859. doi: 10.3390/biology11060859.
The field of natriuretic peptides (NPs) as an endocrine hormone has been developing since 1979. There are three peptides in humans: atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP), which bind to the guanylyl cyclase-A (GC-A) receptor (also called natriuretic peptide receptor-A (NPR-A)), and C-type natriuretic peptide (CNP), which binds to the GC-B receptor (also called the NPR-B) and then synthesizes intracellular cGMP. GC-A receptor stimulation has natriuretic, vasodilatory, cardiorenal protective and anti-renin-angiotensin-aldosterone system actions, and GC-B receptor stimulation can suppress myocardial fibrosis and can activate bone growth before epiphyseal plate closure. These physiological effects are useful as therapeutics for some disease states, such as heart failure, hypertension, and dwarfism. To optimize the therapeutics for each disease state, we must consider drug metabolism, delivery systems, and target receptor(s). We review the cardiac NP system; new designer NPs, such as modified/combined NPs and modified peptides that can bind to not only NP receptors but receptors for other systems; and oral drugs that enhance endogenous NP activity. Finally, we discuss prospective drug discoveries and the development of novel NP therapeutics.
自1979年以来，作为一种内分泌激素的利钠肽（NP）领域一直在发展。人体内有三种肽：心房利钠肽（ANP）和B型利钠肽（BNP），它们与鸟苷酸环化酶-A（GC-A）受体（也称为利钠肽受体-A（NPR-A））结合，以及C型利钠肽（CNP），它与GC-B受体（也称为NPR-B）结合，然后合成细胞内cGMP。GC-A受体刺激具有利钠、血管舒张、心肾保护和抗肾素-血管紧张素-醛固酮系统的作用，而GC-B受体刺激可以抑制心肌纤维化，并在骨骺板闭合前激活骨骼生长。这些生理效应可作为某些疾病状态的治疗方法，如心力衰竭、高血压和侏儒症。为了优化针对每种疾病状态的治疗方法，我们必须考虑药物代谢、给药系统和靶受体。我们综述了心脏NP系统；新型设计NP，如修饰/组合NP以及不仅能与NP受体结合还能与其他系统受体结合的修饰肽；以及增强内源性NP活性的口服药物。最后，我们讨论了前瞻性药物发现和新型NP治疗方法的开发。
