| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Program in Membrane Biology and Renal Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA02114, USA
* To whom correspondence should be addressed. E-mail: brown{at}receptor.mgh.harvard.edu.
Vasopressin-stimulated insertion of the aquaporin 2 water channel into the plasma membrane of kidney collecting duct principal cells is a key event in the urinary concentrating mechanism. The paradigm for vasopressin-receptor signaling involves cAMP-mediated protein kinase A activation, which results in the functionally critical phosphorylation of AQP2 on amino acid serine 256. We previously showed that a parallel cGMP-mediated signaling pathway also leads to AQP2 membrane insertion in AQP2-transfected LLC-PK1 (LLC-AQP2) cells and in outer medullary collecting duct principal cells in situ. In the present report, we show by immunofluorescence microscopy, and Western blotting of plasma membrane fractions, that 45 min exposure of LLC-AQP2 cells to the cGMP phosphodiesterase type 5 (PDE5) inhibitors sildenafil citrate (Viagra®) or 4-{[3',4'-methylene-dioxybenzyl]amino}-6-methoxyquinazoline (MBMQ) elevates intracellular cGMP levels and results in the plasma membrane accumulation of AQP2 - i. e., they mimic the vasopressin effect. Importantly, our data also show that acute exposure to PDE5 inhibitors for 60 min induces apical accumulation of AQP2 in kidney medullary collecting duct principal cells both in tissue slices incubated in vitro, as well as in vivo following intravenous injection of Viagra® into rats. These data suggest that AQP2 membrane insertion can be induced independently of vasopressin-receptor activation, by activating a parallel cGMP-mediated signal transduction pathway with cGMP PDE inhibitors. These results provide proof-of-principle that pharmacological activation of vasopressin- independent, cGMP signaling pathways could aid in the treatment of those forms of nephrogenic diabetes insipidus that are due to vasopressin-2 receptor dysfunction.
This article has been cited by other articles:
|
|
 |
|
  J. Klokkers, P. Langehanenberg, B. Kemper, S. Kosmeier, G. von Bally, C. Riethmuller, F. Wunder, A. Sindic, H. Pavenstadt, E. Schlatter, et al. Atrial natriuretic peptide and nitric oxide signaling antagonizes vasopressin-mediated water permeability in inner medullary collecting duct cells Am J Physiol Renal Physiol, September 1, 2009; 297(3): F693 - F703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Boone, M. Kortenoeven, J. H. Robben, and P. M. T. Deen Effect of the cGMP pathway on AQP2 expression and translocation: potential implications for nephrogenic diabetes insipidus Nephrol. Dial. Transplant., August 8, 2009; (2009) gfp409v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Nunes, U. Hasler, M. McKee, H. A. J. Lu, R. Bouley, and D. Brown A fluorimetry-based ssYFP secretion assay to monitor vasopressin-induced exocytosis in LLC-PK1 cells expressing aquaporin-2 Am J Physiol Cell Physiol, December 1, 2008; 295(6): C1476 - C1487. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Uawithya, T. Pisitkun, B. E. Ruttenberg, and M. A. Knepper Transcriptional profiling of native inner medullary collecting duct cells from rat kidney Physiol Genomics, January 17, 2008; 32(2): 229 - 253. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Vossenkamper, P. I. Nedvetsky, B. Wiesner, J. Furkert, W. Rosenthal, and E. Klussmann Microtubules are needed for the perinuclear positioning of aquaporin-2 after its endocytic retrieval in renal principal cells Am J Physiol Cell Physiol, September 1, 2007; 293(3): C1129 - C1138. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. H. Robben, N. V. A. M. Knoers, and P. M. T. Deen Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol, August 1, 2006; 291(2): F257 - F270. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Zaki, T. Schoneberg, T. Al Ajrawi, A. N. Al Said, K. Sangkuhl, and H. Rompler Nephrogenic diabetes insipidus, thiazide treatment and renal cell carcinoma Nephrol. Dial. Transplant., April 1, 2006; 21(4): 1082 - 1086. [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Bichet Lithium, Cyclic AMP Signaling, A-Kinase Anchoring Proteins, and Aquaporin-2 J. Am. Soc. Nephrol., April 1, 2006; 17(4): 920 - 922. [Full Text] [PDF]
|
|
|
|
|
|
W. Wang, C. Li, L. N. Nejsum, H. Li, S. W. Kim, T.-H. Kwon, T. E. N. Jonassen, M. A. Knepper, K. Thomsen, J. Frokiaer, et al. Biphasic effects of ANP infusion in conscious, euvolumic rats: roles of AQP2 and ENaC trafficking Am J Physiol Renal Physiol, February 1, 2006; 290(2): F530 - F541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Highlights from the Literature Physiology, December 1, 2005; 20(6): 369 - 373. [Full Text] [PDF]
|
|
|
|
|
|
Highlights from the Literature Physiology, October 1, 2005; 20(5): 287 - 291. [Full Text] [PDF]
|
|
|
|
|
|
T. M. Fujiwara and D. G. Bichet Molecular Biology of Hereditary Diabetes Insipidus J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2836 - 2846. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
