| First Author | Thumova M | Year | 2012 |
| Journal | Am J Physiol Renal Physiol | Volume | 303 |
| Issue | 6 | Pages | F812-20 |
| PubMed ID | 22811483 | Mgi Jnum | J:188507 |
| Mgi Id | MGI:5440790 | Doi | 10.1152/ajprenal.00577.2011 |
| Citation | Thumova M, et al. (2012) Pendrin protein abundance in the kidney is regulated by nitric oxide and cAMP. Am J Physiol Renal Physiol 303(6):F812-20 |
| abstractText | Pendrin is a Cl(-)/HCO(3)(-) exchanger, expressed in the apical regions of some intercalated cell subtypes, and is critical in the pressor response to angiotensin II. Since angiotensin type 1 receptor inhibitors reduce renal pendrin protein abundance in mice in vivo through a mechanism that is dependent on nitric oxide (NO), we asked if NO modulates renal pendrin expression in vitro and explored the mechanism by which it occurs. Thus we quantified pendrin protein abundance by confocal fluorescent microscopy in cultured mouse cortical collecting ducts (CCDs) and connecting tubules (CNTs). After overnight culture, CCDs maintain their tubular structure and maintain a solute gradient when perfused in vitro. Pendrin protein abundance increased 67% in CNT and 53% in CCD when NO synthase was inhibited (N(G)-nitro-l-arginine methyl ester, 100 muM), while NO donor (DETA NONOate, 200 muM) application reduced pendrin protein by approximately 33% in the CCD and CNT. When CNTs were cultured in the presence of the guanylyl cyclase inhibitor 1H-[1,2,4] oxadiazolo[4,3-a]quinoxalin-1-one (10 muM), NO donors did not alter pendrin abundance. Conversely, pendrin protein abundance rose when cAMP content was increased by the application of an adenylyl cyclase agonist (forskolin, 10 muM), a cAMP analog (8-bromo-cAMP, 1 mM), or a phosphodiesterase inhibitor (BAY60-7550, 50 muM). Since NO reduces cellular cAMP in the CNT, we asked if NO reduces pendrin abundance by reducing cAMP. With blockade of cGMP-stimulated phosphodiesterase II, NO did not alter pendrin protein abundance. We conclude that NO acts through cAMP to reduce pendrin total protein abundance by enhancing cAMP degradation. |
