| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, Emory University, Atlanta, Georgia, United States
2 Renal Division, Department of Medicine, Emory University, Atlanta, Georgia, United States
3 Renal Division, Department of Medicine, Emory University, Atlanta, Georgia, United States; Department of Physiology, Emory University, Atlanta, Georgia, United States
* To whom correspondence should be addressed. E-mail: froehlich{at}physio.emory.edu.
Trans-epithelial 14C-urea fluxes were measured across cultured MDCK cells permanently transfected to express the urea transport protein UT-A1. The urea fluxes were typically increased from a basal rate of 2 to 10 and 25 nmol cm-2min-1 in the presence of vasopressin and forskolin, respectively. Flux activation consisted of a rapid-onset component of small amplitude that leveled off within about 10 min and at times even decreased again, followed by a delayed, strong increase over the next 30-40 min. Forskolin activated urea transport through activation of adenylyl cyclase; dideoxyforskolin was inactive. Vasopressin activated urea transport only from the basolateral side and was blocked by OPC-31260, indicating that its action was mediated by basolateral V2-receptors. In the presence of the phosphodiesterase inhibitor IBMX, vasopressin activated as strongly as forskolin. By itself, IBMX caused a slow increase over 50 min to about 5 nmol cm-2min-1. 8-Br-cAMP (at 300 µM) activated urea flux only when added basolaterally. IBMX augmented the activation by basolateral 8-Br-cAMP. Urea flux activation by vasopressin and forskolin were only partially blocked by the protein kinase A inhibitor, H-89. Even at concentrations above 10 µM, urea flux after 60 min of stimulation was reduced by less than 50%. The rapid-onset component appeared unaffected by the presence of H-89. These data suggest that activation of transepithelial urea transport across MDCK-UT-A1 cells by forskolin and vasopressin involves cAMP as a second messenger and that it is mediated by one or more signaling pathways separate from and in addition to protein kinase A.
This article has been cited by other articles:
|
|
 |
|
  Y. Wang, J. D. Klein, M. A. Blount, C. F. Martin, K. J. Kent, V. Pech, S. M. Wall, and J. M. Sands Epac Regulates UT-A1 to Increase Urea Transport in Inner Medullary Collecting Ducts J. Am. Soc. Nephrol., September 1, 2009; 20(9): 2018 - 2024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Mistry, R. Mallick, J. D. Klein, T. Weimbs, J. M. Sands, and O. Frohlich Syntaxin specificity of aquaporins in the inner medullary collecting duct Am J Physiol Renal Physiol, August 1, 2009; 297(2): F292 - F300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Hasler Controlled aquaporin-2 expression in the hypertonic environment Am J Physiol Cell Physiol, April 1, 2009; 296(4): C641 - C653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Stewart, A. Thistlethwaite, H. Lees, G. J. Cooper, and C. Smith Vasopressin regulation of the renal UT-A3 urea transporter Am J Physiol Renal Physiol, March 1, 2009; 296(3): F642 - F648. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. W. Blessing, M. A. Blount, J. M. Sands, C. F. Martin, and J. D. Klein Urea transporters UT-A1 and UT-A3 accumulate in the plasma membrane in response to increased hypertonicity Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1336 - F1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen, H. Huang, O. Frohlich, Y. Yang, J. D. Klein, S. R. Price, and J. M. Sands MDM2 E3 ubiquitin ligase mediates UT-A1 urea transporter ubiquitination and degradation Am J Physiol Renal Physiol, November 1, 2008; 295(5): F1528 - F1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Blount, A. C. Mistry, O. Frohlich, S. R. Price, G. Chen, J. M. Sands, and J. D. Klein Phosphorylation of UT-A1 urea transporter at serines 486 and 499 is important for vasopressin-regulated activity and membrane accumulation Am J Physiol Renal Physiol, July 1, 2008; 295(1): F295 - F299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Frohlich, D. Aggarwal, J. D. Klein, K. J. Kent, Y. Yang, R. B. Gunn, and J. M. Sands Stimulation of UT-A1-mediated transepithelial urea flux in MDCK cells by lithium Am J Physiol Renal Physiol, March 1, 2008; 294(3): F518 - F524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Blount, J. D. Klein, C. F. Martin, D. Tchapyjnikov, and J. M. Sands Forskolin stimulates phosphorylation and membrane accumulation of UT-A3 Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1308 - F1313. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Fenton and M. A. Knepper Urea and Renal Function in the 21st Century: Insights from Knockout Mice J. Am. Soc. Nephrol., March 1, 2007; 18(3): 679 - 688. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
