| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, USA
* To whom correspondence should be addressed. E-mail: phofmann{at}physio1.utmem.edu.
Adenosine A1 receptor activation causes protein phosphatase 2a (PP2a) activation in ventricular myocytes. This attenuates beta-adrenergic functional effects in the heart (Liu and Hofmann, Am J Physiol 283: H1314-21, 2002). The purpose of the present study was to identify the signaling pathway involved in the translocation/activation of PP2a by adenosine A1 receptors in ventricular myocytes. We found N6-cyclopentyladenosine (CPA; adenosine A1 receptor agonist)-induced PP2a translocation was blocked by p38 MAPK inhibition, but not by JNK inhibition. CPA increased phosphorylation of p38 MAPK and this effect was abolished by pertussis toxin and inhibitors of the cyclic GMP pathway. Moreover, CPA-induced PP2a translocation was blocked by inhibition of the cyclic GMP pathway. Guanylyl cyclase activation mimicked the effects of CPA and caused p38 MAPK phosphorylation and PP2a translocation. Finally, CPA-induced dephosphorylations of troponin I and phospholamban were blocked by pertussis toxin and attenuated by p38 MAPK inhibition. These results suggest adenosine A1 receptor-mediated PP2a activation uses a pertussis toxin sensitive Gi protein-guanylyl cyclase-p38 MAPK pathway. This proposed, novel pathway may play a role in acute modulation of cardiac function.
This article has been cited by other articles:
|
|
 |
|
  M. Kurdi and G. W. Booz JAK redux: a second look at the regulation and role of JAKs in the heart Am J Physiol Heart Circ Physiol, November 1, 2009; 297(5): H1545 - H1556. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Szokodi, R. Kerkela, A.-M. Kubin, B. Sarman, S. Pikkarainen, A. Konyi, I. G. Horvath, L. Papp, M. Toth, R. Skoumal, et al. Functionally Opposing Roles of Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase in the Regulation of Cardiac Contractility Circulation, October 14, 2008; 118(16): 1651 - 1658. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Leary, S. Rajasekaran, R. R. Morrison, E. I. Tuomanen, T. K. Chin, and P. A. Hofmann A cardioprotective role for platelet-activating factor through NOS-dependent S-nitrosylation Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2775 - H2784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Junttila, S.-P. Li, and J. Westermarck Phosphatase-mediated crosstalk between MAPK signaling pathways in the regulation of cell survival FASEB J, April 1, 2008; 22(4): 954 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ballard-Croft, A. C. Locklar, B. J. Keith, R. M. Mentzer Jr, and R. D. Lasley Oxidative stress and adenosine A1 receptor activation differentially modulate subcellular cardiomyocyte MAPKs Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H263 - H271. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. A. Hofmann, M. Israel, Y. Koseki, J. Laskin, J. Gray, A. Janik, T. W. Sweatman, and L. Lothstein N-Benzyladriamycin-14-valerate (AD 198): A Non-Cardiotoxic Anthracycline That Is Cardioprotective through PKC-{epsilon} Activation J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 658 - 664. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Cheng, J. Liu, M. Asuncion-Chin, E. Blaskova, J. P. Bannister, A. M. Dopico, and J. H. Jaggar A Novel CaV1.2 N Terminus Expressed in Smooth Muscle Cells of Resistance Size Arteries Modifies Channel Regulation by Auxiliary Subunits J. Biol. Chem., October 5, 2007; 282(40): 29211 - 29221. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. A. Sheehan, Y. Ke, and R. J. Solaro p21-Activated kinase-1 and its role in integrated regulation of cardiac contractility Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R963 - R973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Reichelt, L. Willems, J. N. Peart, K. J. Ashton, G. P. Matherne, M. R. Blackburn, and J. P. Headrick Heart/Cardiac Muscle: Modulation of ischaemic contracture in mouse hearts: a 'supraphysiological' response to adenosine Exp Physiol, January 1, 2007; 92(1): 175 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Y. Tan, C. L. Richard, H. Zhang, D. W. Hoskin, and J. Blay Adenosine downregulates DPPIV on HT-29 colon cancer cells by stimulating protein tyrosine phosphatase(s) and reducing ERK1/2 activity via a novel pathway Am J Physiol Cell Physiol, September 1, 2006; 291(3): C433 - C444. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Snabaitis, R. D'Mello, S. Dashnyam, and M. Avkiran A Novel Role for Protein Phosphatase 2A in Receptor-mediated Regulation of the Cardiac Sarcolemmal Na+/H+ Exchanger NHE1 J. Biol. Chem., July 21, 2006; 281(29): 20252 - 20262. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. I. Tikh, R. A. Fenton, and J. G. Dobson Jr. Contractile effects of adenosine A1 and A2A receptors in isolated murine hearts Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H348 - H356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. Lasley, B. J. Keith, G. Kristo, Y. Yoshimura, and R. M. Mentzer Jr. Delayed adenosine A1 receptor preconditioning in rat myocardium is MAPK dependent but iNOS independent Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H785 - H791. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Gigena, A. Ito, H. Nojima, and T. B. Rogers A B56 regulatory subunit of protein phosphatase 2A localizes to nuclear speckles in cardiomyocytes Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H285 - H294. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Ballard-Croft, G. Kristo, Y. Yoshimura, E. Reid, B. J. Keith, R. M. Mentzer Jr., and R. D. Lasley Acute adenosine preconditioning is mediated by p38 MAPK activation in discrete subcellular compartments Am J Physiol Heart Circ Physiol, March 1, 2005; 288(3): H1359 - H1366. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hersch, J. Huang, J. R. Grider, and K. S. Murthy Gq/G13 signaling by ET-1 in smooth muscle: MYPT1 phosphorylation via ETA and CPI-17 dephosphorylation via ETB Am J Physiol Cell Physiol, November 1, 2004; 287(5): C1209 - C1218. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Liu and P. A. Hofmann Protein phosphatase 2A-mediated cross-talk between p38 MAPK and ERK in apoptosis of cardiac myocytes Am J Physiol Heart Circ Physiol, June 1, 2004; 286(6): H2204 - H2212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Schulz and G. Heusch Connexin 43 and ischemic preconditioning Cardiovasc Res, May 1, 2004; 62(2): 335 - 344. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Metzger and M. V. Westfall Covalent and Noncovalent Modification of Thin Filament Action: The Essential Role of Troponin in Cardiac Muscle Regulation Circ. Res., February 6, 2004; 94(2): 146 - 158. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
