Department of Psychiatry and Behavioral Sciences, University of Louisville, Louisville, Kentucky, United States of America.
Department of Physiology, School of Medicine, University of Maryland, Baltimore, Mississippi, United States of America.
PLoS One. 2021 Nov 18;16(11):e0260131. doi: 10.1371/journal.pone.0260131. eCollection 2021.
Endogenous ouabain (EO) and atrial natriuretic peptide (ANP) are important in regulation of sodium and fluid balance. There is indirect evidence that ANP may be involved in the regulation of endogenous cardenolides.
H295R are human adrenocortical cells known to release EO. Cells were treated with ANP at physiologic concentrations or vehicle (0.1% DMSO), with or without guanylyl cyclase inhibitor 1,2,4 oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cyclic guanosine monophosphate (cGMP), the intracellular second messenger of ANP, was measured by a chemiluminescent immunoassay and EO was measured by radioimmunoassay of C18 extracted samples.
EO secretion is inhibited by ANP treatment, with the most prolonged inhibition (90 min vs ≤ 60 min) occurring at physiologic ANP concentrations (50 pg/mL). Inhibition of guanylyl cyclase with ODQ, also reduces EO secretion. The inhibitory effects on EO release in response to cotreatment with ANP and ODQ appeared to be additive.
ANP inhibits basal EO secretion, and it is unlikely that this is mediated through ANP-A or ANP-B receptors (the most common natriuretic peptide receptors) or their cGMP second messenger; the underlying mechanisms involved are not revealed in the current studies. The role of ANP in the control of EO synthesis and secretion in vivo requires further investigation.
内源性哇巴因（EO）和心钠肽（ANP）在调节钠和液体平衡方面很重要。有间接证据表明，ANP 可能参与内源性卡烯内酯的调节。
H295R 是人肾上腺皮质细胞，已知会释放 EO。用生理浓度的 ANP 或载体（0.1% DMSO）处理细胞，有或没有鸟苷酸环化酶抑制剂 1,2,4 恶二唑[4,3-a]喹喔啉-1-酮（ODQ）。用化学发光免疫分析法测定 ANP 的细胞内第二信使环鸟苷酸（cGMP），用 C18 提取样品的放射免疫法测定 EO。
ANP 处理抑制 EO 分泌，生理浓度的 ANP（50 pg/mL）作用下抑制作用最长（90 分钟对≤60 分钟）。用 ODQ 抑制鸟苷酸环化酶也会减少 EO 的分泌。用 ANP 和 ODQ 共同处理对 EO 释放的抑制作用似乎是累加的。
ANP 抑制基础 EO 分泌，这不太可能是通过 ANP-A 或 ANP-B 受体（最常见的利钠肽受体）或其 cGMP 第二信使介导的；目前的研究没有揭示涉及的潜在机制。ANP 在体内控制 EO 合成和分泌的作用需要进一步研究。
