| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Molecular Pharmacology and Physiology, University of South Florida, Tampa, Florida, United States
* To whom correspondence should be addressed. E-mail: dyip{at}health.usf.edu.
PKA has traditionally been thought as the binding protein of cAMP for mediating arginine vasopressin (AVP) regulated osmotic water permeability in kidney collecting duct. It is now known that cAMP also exerts its effects via Epac (exchange protein directly activated by cAMP), and that intracellular Ca2+ mobilization is necessary for AVP induced apical exocytosis in inner medullary collecting duct (IMCD). The role of Epac as an effector of cAMP action in addition to PKA was investigated using confocal fluorescence microscopy in perfused IMCD. PKA inhibitors (1 µM H-89 or 10 µM KT5720) at concentrations known to inhibit aquaporin-2 (AQP2) phosphorylation did not prevent AVP induced Ca2+ mobilization and oscillations. Epac selective cAMP agonist (8-pCPT-2'-O-Me-cAMP) mimicked AVP in triggering Ca2+ mobilization and oscillations, which was blocked by ryanodine but not by Rp-cAMP (a competitive antagonist of cAMP binding to PKA). 8-pCPT-2'-O-Me-cAMP also triggered apical exocytosis in the presence of PKA inhibitor. Immunolocalization of AQP2 in perfused IMCD demonstrated that 8-pCPT-2'-O-Me-cAMP induces apical targeting of AQP2, and that AQP2 is abundant in junctional regions of basolateral membrane. Immunofluorescence study also confirmed the presence of Epac (isoform I) in IMCD. These results indicate that activation of Epac by exogenous cAMP analog triggers [Ca2+ ]i mobilization and apical exocytotic insertion of AQP2 in IMCD.
This article has been cited by other articles:
|
|
 |
|
  P. S. Caceres, G. R. Ares, and P. A. Ortiz cAMP Stimulates Apical Exocytosis of the Renal Na+-K+-2Cl- Cotransporter NKCC2 in the Thick Ascending Limb: ROLE OF PROTEIN KINASE A J. Biol. Chem., September 11, 2009; 284(37): 24965 - 24971. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. I. Purves, T. Kamishima, L. M. Davies, J. M. Quayle, and C. Dart Exchange protein activated by cAMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP-sensitive potassium channels J. Physiol., July 15, 2009; 587(14): 3639 - 3650. [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]
|
|
|
|
 |
|
 Y. Li, I. B. M. Konings, J. Zhao, L. S. Price, E. de Heer, and P. M. T. Deen Renal expression of exchange protein directly activated by cAMP (Epac) 1 and 2 Am J Physiol Renal Physiol, August 1, 2008; 295(2): F525 - F533. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Kang, C. A. Leech, O. G. Chepurny, W. A. Coetzee, and G. G. Holz Role of the cAMP sensor Epac as a determinant of KATP channel ATP sensitivity in human pancreatic {beta}-cells and rat INS-1 cells J. Physiol., March 1, 2008; 586(5): 1307 - 1319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. M. Pastor-Soler, K. R. Hallows, C. Smolak, F. Gong, D. Brown, and S. Breton Alkaline pH- and cAMP-induced V-ATPase membrane accumulation is mediated by protein kinase A in epididymal clear cells Am J Physiol Cell Physiol, February 1, 2008; 294(2): C488 - C494. [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]
|
|
|
|
 |
|
 B. J. Aragona and Z. Wang Opposing Regulation of Pair Bond Formation by cAMP Signaling within the Nucleus Accumbens Shell J. Neurosci., November 28, 2007; 27(48): 13352 - 13356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Goel, W. G. Sinkins, C.-D. Zuo, U. Hopfer, and W. P. Schilling Vasopressin-induced membrane trafficking of TRPC3 and AQP2 channels in cells of the rat renal collecting duct Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1476 - F1488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Fenton and M. A. Knepper Mouse Models and the Urinary Concentrating Mechanism in the New Millennium Physiol Rev, October 1, 2007; 87(4): 1083 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. A. Fenton, L. Brond, S. Nielsen, and J. Praetorius Cellular and subcellular distribution of the type-2 vasopressin receptor in the kidney Am J Physiol Renal Physiol, September 1, 2007; 293(3): F748 - F760. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ulucan, X. Wang, E. Baljinnyam, Y. Bai, S. Okumura, M. Sato, S. Minamisawa, S. Hirotani, and Y. Ishikawa Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1662 - H1672. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. O'Connor and A. W. Cowley Jr. Vasopressin-induced nitric oxide production in rat inner medullary collecting duct is dependent on V2 receptor activation of the phosphoinositide pathway Am J Physiol Renal Physiol, August 1, 2007; 293(2): F526 - F532. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. G. Holz, G. Kang, M. Harbeck, M. W. Roe, and O. G. Chepurny Cell physiology of cAMP sensor Epac J. Physiol., November 15, 2006; 577(1): 5 - 15. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
