Premium
Downregulation of natriuretic peptide clearance receptor mRNA in vascular smooth muscle cells by angiotensin II
Author(s) -
Jiao Yuhang,
Yang Qing
Publication year - 2015
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12111
Subject(s) - protein kinase c , angiotensin ii , endocrinology , downregulation and upregulation , medicine , angiotensin ii receptor type 1 , angiotensin receptor , chelerythrine , vascular smooth muscle , losartan , tyrosine kinase , atrial natriuretic peptide , renin–angiotensin system , protein kinase a , chemistry , receptor , phorbol , signal transduction , biology , kinase , biochemistry , smooth muscle , gene , blood pressure
Angiotensin II can downregulate atrial natriuretic peptide binding to rat vascular smooth muscle cells ( VSMC s), but the mechanism is not known. Because protein kinase C ( PKC ) mimetic phorbol myristate acetate ( PMA ) can destabilize natriuretic peptide clearance receptor ( NPR ‐C) mRNA and angiotensin II activates several PKC isoforms in VSMCs, we hypothesized that angiotensin II treatment decreases NPR ‐C mRNA stability and exerts this effect through PKC . This study demonstrated that angiotensin II induced time‐ and concentration‐dependent downregulation of NPR ‐C, which was completely inhibited by an angiotensin II type I receptor blocker losartan. NPR ‐C mRNA disappearance rate over 6 h was nearly doubled by exposure of VSMCs to 100 n m angiotensin II , compared with that observed after inhibition of RNA synthesis alone. However, this response to angiotensin II was undiminished by the PKC inhibitor chelerythrine, or by depletion of PKC by prior exposure of cells to PMA for 48 h. Inhibitors of tyrosine kinases, phospholipase C, or mitogen‐activated protein kinase kinase also failed to reverse the angiotensin II effect. We conclude that at least two distinct proximal signaling pathways, one involved and one independent of phorbol ester‐sensitive protein kinase C, lead to downregulation of NPR ‐C gene expression by destabilizing its mRNA.