Hypertension. 2005;46:628-634
Published online before print August 15, 2005,
doi: 10.1161/01.HYP.0000178464.63393.88
(Hypertension. 2005;46:628.)
© 2005 American Heart Association, Inc.
Adenosine Inhibits PDGF-Induced Growth of Human Glomerular Mesangial Cells Via A2B Receptors
Raghvendra K. Dubey;
Delbert G. Gillespie;
Zaichuan Mi;
Edwin K. Jackson
From the Center for Clinical Pharmacology, Departments of Medicine (R.K.D., D.G.G., Z.M., E.K.J.) and Pharmacology (E.K.J.), University of Pittsburgh Medical Center, Pittsburgh, Pa, and the Clinic for Endocrinology (R.K.D.), Department of Obstetrics and Gynecology, University Hospital Zurich, Zurich, Switzerland.
Correspondence to Dr Raghvendra K. Dubey, Department of Obstetrics and Gynecology Clinic for Endocrinology, D215 NORD-1, Frauenklinik University Hospital Zurich, 8091 Zurich, Switzerland. E-mail Raghvendra.dubey{at}usz.ch
The objectives of the present study were to determine whether adenosine attenuates proliferation of glomerular mesangial cells (GMCs), which adenosine receptor (AR) mediates the antimitogeneic actions of adenosine, and the cellular mechanisms by which adenosine inhibits growth of GMCs. Studies were conducted in both human and rat GMCs. Platelet-derived growth factor (PDGF)-BB (25 ng/mL) increased DNA synthesis ([3H]thymidine incorporation), cellular proliferation (cell number), collagen synthesis ([3H]proline incorporation), and mitogen-activated protein kinase (MAPK) activity, and these effects were attenuated by 2-chloroadenosine (nonselective AR agonist) and 5'-N-methylcarboxamidoadenosine (MECA; nonselective AR agonist), but not by N6-cyclopentyladenosine (selective A1 AR agonist), AB-N-MECA (selective A3 AR agonist), or CGS21680(selective A2A AR agonist). KF17837 (selective A2A/B AR antagonist) and 1,3-dipropyl-8-p-sulfophenylxanthine (nonselective AR antagonist), but not 8-cyclopentyl-1,3-dipropylxanthine (selective A1 AR antagonist), blocked the growth-inhibitory effects of 2-chloroadenosine and 5'-N-MECA. Antisense, but not sense or scrambled, oligonucleotides to the A2B receptor increased both basal and PDGF-induced DNA synthesis, cell proliferation, and collagen synthesis, and the growth-inhibitory effects of 2-chloroadenosine, 5'-N-MECA, and erythro-9-(2-hydroxy-3-nonyl)adenine (inhibitor of adenosine deaminase) plus iodotubercidin (inhibitor of adenosine kinase) were abolished by antisense, but not scrambled or sense, oligonucleotides to the A2B receptor. We conclude that adenosine causes inhibition of GMC growth by activating A2B receptors coupled to inhibition of MAPK activity. A2B receptors may play an important role in regulating glomerular remodeling associated with GMC proliferation. Pharmacological or molecular biologic activation of A2B receptors may prevent glomerular remodeling associated with glomerulosclerosis, renal disease, and abnormal growth associated with hypertension and diabetes.
Key Words: adenosine mesangium receptors, adenine remodeling glomerulosclerosis renal disease kidney
This article has been cited by other articles:

|
 |

|
 |
 
J. Ren, Z. Mi, and E. K. Jackson
Assessment of Nerve Stimulation-Induced Release of Purines from Mouse Kidneys by Tandem Mass Spectrometry
J. Pharmacol. Exp. Ther.,
June 1, 2008;
325(3):
920 - 926.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. K. Jackson, Z. Mi, and R. K. Dubey
The Extracellular cAMP-Adenosine Pathway Significantly Contributes to the in Vivo Production of Adenosine
J. Pharmacol. Exp. Ther.,
January 1, 2007;
320(1):
117 - 123.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Wakeno, T. Minamino, O. Seguchi, H. Okazaki, O. Tsukamoto, K.-i. Okada, A. Hirata, M. Fujita, H. Asanuma, J. Kim, et al.
Long-Term Stimulation of Adenosine A2b Receptors Begun After Myocardial Infarction Prevents Cardiac Remodeling in Rats
Circulation,
October 31, 2006;
114(18):
1923 - 1932.
[Abstract]
[Full Text]
[PDF]
|
 |
|