Key result
Incubation of freshly isolated human proximal tubular cells with exogenous ANP, BNP, CNP, or C(4.23)ANF induced expression of functionally active NPR-A and NPR-B receptors, likely mediated via NPR-C.
In human proximal tubular cells, the development of functionally active NPR-A and -B receptors is linked to increased expression of natriuretic peptides, likely mediated via the NPR-C receptor.
May modulate natriuretic signaling in renal tubules via NPR-C; hypothesis-generating for hypertension therapies, needs in vivo confirmation.
INTRODUCTION: 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). OBJECTIVE: 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. RESULTS: 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. CONCLUSIONS: 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.
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Mistry et al. (2001) studied this question. Exogenous ANP, BNP, CNP or NPR-C specific ligand C(4.23)ANF vs. Freshly isolated cells was evaluated on Expression of natriuretic peptide receptors (NPR-A, -B, -C). Incubation of freshly isolated human proximal tubular cells with exogenous ANP, BNP, CNP, or C(4.23)ANF induced expression of functionally active NPR-A and NPR-B receptors, likely mediated via NPR-C.
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