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Calcineurin Mediates Natriuretic Peptide Receptor‐A Desensitization in MA‐10 Cells
Author(s) -
Henesy Michelle B,
Rich Thomas C
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.888.2
Subject(s) - homologous desensitization , calcineurin , heterologous , dephosphorylation , desensitization (medicine) , phosphatase , intracellular , chemistry , receptor , endocrinology , medicine , homologous chromosome , microbiology and biotechnology , biology , biochemistry , enzyme , transplantation , gene
Natriuretic peptides (e.g., ANP) activate particulate guanylyl cyclases (e.g. NPR‐A) leading to increased intracellular cGMP. Cellular mechanisms underlying the regulation of NPR‐A are poorly understood. It is known that both homologous and heterologous NPR‐A desensitization result in decreased guanylyl cyclase activity correlating with loss of phosphate. The phosphatase responsible for NPR‐A desensitization has not been identified. Here we identify the phosphatase responsible for both homologous and heterologous NPR‐A desensitization in murine leydig tumor cells. We measured ANP‐induced increases in intracellular cGMP levels in the presence and absence of an array of phosphatase inhibitors and following si‐RNA‐mediated knockdown of calcineurin. Results suggest that calcineurin (PP2B) is primarily responsible for both homologous and heterologous desensitization. In addition, we observed that calcinuerin inhibitors attenuate ANP‐induced loss of phosphate from NPR‐A. Taken together, these data suggest that calcineurin is the phosphatase primarily responsible for dephosphorylation and subsequent desensitization of NPR‐A. Supported by AHA 0715101B and 0335084N, NIH HL74278.