Differential expression and synthesis of natriuretic peptides determines natriuretic peptide receptor expression in primary cultures of human proximal tubular cells

Introduction The natriuretic peptides and natriuretic peptide receptors may play a beneficial role in hypertension and heart failure and possibly in o pposing associated detrimental cellular changes in the heart, vasculature a nd kidney. These responses may be, in part, modulated by the natriuretic pe ptide clearance receptor rather than the natriuretic peptide receptors (NPR -A or NPR-B), Objective To investigate the expression of the natriuretic peptide receptor s (NPR-A,-B,-C) and the natriuretic peptides (ANP, BNP, CNP) in primary cul tures of human proximal tubular cells and the role played by endogenously r eleased natriuretic peptides in natriuretic peptide receptor expression. Results Northern analysis demonstrated that freshly isolated human proximal tubular cells express the NPR-C only. However, at confluence mRNA transcri pts for both the NPR-A and -B were expressed, accompanied by a significant cyclic guanosine monophosphate (cGMP) response to ANP and CNP, indicating t he development of functionally active receptors, A significant increase in immunoreactive ANP, BNP and CNP in the cell supernatant accompanied the app earance of these receptors. incubation of freshly isolated cells with exoge nous ANP, BNP, CNP or with the NPR-C specific ligand C((4-23))ANF induced s imilar changes in receptor expression, suggesting that these changes were m ediated via the NPR-C rather than the NPR-A or -B, Conclusions Significant changes in peptide and receptor expression occur du ring cell culture and may be integrally linked, with functionally active NP R-A and -B occurring in response to an increase in the expression of the na triuretic peptides possibly acting at the NPR-C. (C) 2001 Lippincott Willia ms & Wilkins.