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Publication : Altered expression of natriuretic peptide receptors in proANP gene disrupted mice.

First Author  Vera N Year  2000
Journal  Cardiovasc Res Volume  46
Issue  3 Pages  595-603
PubMed ID  10912470 Mgi Jnum  J:84437
Mgi Id  MGI:2667589 Doi  10.1016/s0008-6363(00)00038-9
Citation  Vera N, et al. (2000) Altered expression of natriuretic peptide receptors in proANP gene disrupted mice. Cardiovasc Res 46(3):595-603
abstractText  BACKGROUND: The atrial natriuretic peptide (ANP) family is a complex system consisting of at least three polypeptides and at least three types of receptor. Each peptide interacts with different types of receptor at varying degrees of affinity. To determine if natriuretic peptide levels influence natriuretic peptide receptor expression and regulation, we examined the expression of guanylyl cyclase linked GC-A, GC-B and C-receptor in the lungs of mice with a mutation that inactivates the ANP gene (Nppa). METHODS: The mRNA level of GC-A, GC-B and C-receptor in the lung were studied by ribonuclease protection assays (RPA). RESULTS: Results of RPA showed that although the mRNA level of GC-A and GC-B of heterozygous ANP+/- was not different from wild type ANP+/+ mice, they were significantly higher in the homozygous mutant ANP-/- mice. In addition, C-receptor mRNA level in ANP+/- and ANP-/- was significantly lower than ANP+/+ mice. The C-receptor results were confirmed by receptor binding assays and affinity cross-linking studies. CONCLUSIONS: Taken together these data suggest that permanent removal of ANP from the natriuretic peptide system results in an up-regulation of GC-A and GC-B, and a corresponding down-regulation of C-receptor in the lung of proANP gene disrupted mice. We postulated that changes in the natriuretic peptide receptor population may result in chronic hypertension and cardiac hypertrophy in the ANP-/- mice.
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