Mistry S K, Hawksworth G M, Struthers A D, McLay J S
Department of Medicine and Therapeutics, Aberdeen University Medical School, Foresterhill, UK.
J Hypertens. 2001 Feb;19(2):255-62. doi: 10.1097/00004872-200102000-00012.
The natriuretic peptides and natriuretic peptide receptors may play a beneficial role in hypertension and heart failure and possibly in opposing associated detrimental cellular changes in the heart, vasculature and kidney. These responses may be, in part, modulated by the natriuretic peptide clearance receptor rather than the natriuretic peptide receptors (NPR-A or NPR-B).
To investigate the expression of the natriuretic peptide receptors (NPR-A,-B,-C) and the natriuretic peptides (ANP, BNP, CNP) in primary cultures of human proximal tubular cells and the role played by endogenously released natriuretic peptides in natriuretic peptide receptor expression.
Northern analysis demonstrated that freshly isolated human proximal tubular cells express the NPR-C only. However, at confluence mRNA transcripts for both the NPR-A and -B were expressed, accompanied by a significant cyclic guanosine monophosphate (cGMP) response to ANP and CNP, indicating the development of functionally active receptors. A significant increase in immunoreactive ANP, BNP and CNP in the cell supernatant accompanied the appearance of these receptors. Incubation of freshly isolated cells with exogenous ANP, BNP, CNP or with the NPR-C specific ligand C(4.23)ANF induced similar changes in receptor expression, suggesting that these changes were mediated via the NPR-C rather than the NPR-A or -B.
Significant changes in peptide and receptor expression occur during cell culture and may be integrally linked, with functionally active NPR-A and -B occurring in response to an increase in the expression of the natriuretic peptides possibly acting at the NPR-C.
利钠肽和利钠肽受体可能在高血压和心力衰竭中发挥有益作用，并且可能对抗心脏、血管和肾脏中相关的有害细胞变化。这些反应可能部分由利钠肽清除受体而非利钠肽受体（NPR - A或NPR - B）调节。
研究人近端肾小管细胞原代培养物中利钠肽受体（NPR - A、-B、-C）和利钠肽（心房钠尿肽、脑钠肽、C型钠尿肽）的表达，以及内源性释放的利钠肽在利钠肽受体表达中所起的作用。
Northern分析表明，新鲜分离的人近端肾小管细胞仅表达NPR - C。然而，汇合时NPR - A和 - B的mRNA转录本均有表达，同时对心房钠尿肽和C型钠尿肽有显著的环磷酸鸟苷（cGMP）反应，表明功能性活性受体的形成。这些受体出现的同时，细胞上清液中免疫反应性心房钠尿肽、脑钠肽和C型钠尿肽显著增加。用外源性心房钠尿肽、脑钠肽、C型钠尿肽或NPR - C特异性配体C(4.23)ANF孵育新鲜分离的细胞，可诱导受体表达发生类似变化，提示这些变化是通过NPR - C而非NPR - A或 - B介导的。
细胞培养过程中肽和受体表达发生显著变化，且可能存在整体联系。功能性活性NPR - A和 - B的出现可能是对可能作用于NPR - C的利钠肽表达增加的反应。
