QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.103.057166v1 307/3/888    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Jackson, E. K. Articles by Dubey, R. K. Search for Related Content PubMed PubMed Citation Articles by Jackson, E. K. Articles by Dubey, R. K.

GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

Adenosine Biosynthesis in the Collecting Duct

Center for Clinical Pharmacology (E.K.J., Z.M., C.Z., R.K.D.) and Departments of Medicine (E.K.J., Z.M., C.Z., R.K.D.) and Pharmacology (E.K.J.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and Clinic for Endocrinology, Department of Obstetrics and Gynecology, University Hospital Zurich, Zurich, Switzerland (R.K.D.)

Adenosine regulates tubular transport in collecting ducts (CDs); however, the sources of adenosine that modulate ion transport in CDs are unknown. The extracellular cAMP-adenosine pathway refers to the conversion of cAMP to AMP by ectophosphodiesterase, followed by metabolism of AMP to adenosine by ecto-5'-nucleotidase, with all steps occurring in the extracellular compartment. The goal of this study was to assess whether the extracellular cAMP-adenosine pathway exists in CDs. Studies were conducted in both freshly isolated CDs and in CD cells in culture (first passage) that were derived from isolated CDs. Purity of CDs was confirmed by microscopy, by Western blotting for aquaporin-1, aquaporin-2, bumetanide-sensitive cotransporter type 1, and thiazide-sensitive cotransporter; and by reverse transcription-polymerase chain reaction for adenosine receptors. Both freshly isolated CDs and CD cells in culture converted exogenous cAMP to AMP and adenosine. In both freshly isolated CDs and CD cells in culture, conversion of cAMP to AMP and adenosine was affected by a broad-spectrum phosphodiesterase inhibitor (3-isobutyl-1-methylxanthine), an ectophosphodiesterase inhibitor (1,3-dipropyl-8-p-sulfophenylxanthine), and a blocker of ecto-5'-nucleotidase (,-methylene-adenosine-5'-diphosphate) in a manner consistent with exogenous cAMP being processed by the extracellular cAMP-adenosine pathway. In CD cells in culture, stimulation of adenylyl cyclase increased extracellular concentrations of cAMP, AMP, and adenosine, and these changes were also modulated by the aforementioned inhibitors in a manner consistent with the extracellular cAMP-adenosine pathway. In conclusion, the extracellular cAMP-adenosine pathway is an important source of adenosine in CDs.

Address correspondence to: Dr. Edwin K. Jackson, Center for Clinical Pharmacology, University of Pittsburgh School of Medicine, 623 Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261. E-mail: edj+{at}pitt.edu

This article has been cited by other articles:

				J. Ren, Z. Mi, N. A. Stewart, and E. K. Jackson Identification and Quantification of 2',3'-cAMP Release by the Kidney J. Pharmacol. Exp. Ther., March 1, 2009; 328(3): 855 - 865. [Abstract] [Full Text] [PDF]

				T. Rieg and V. Vallon ATP and adenosine in the local regulation of water transport and homeostasis by the kidney Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2009; 296(2): R419 - R427. [Abstract] [Full Text] [PDF]

				E. K. Jackson and Z. Mi Regulation of Renal Ectophosphodiesterase by Protein Kinase C and Sodium Diet J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 210 - 216. [Abstract] [Full Text] [PDF]

				T. Rieg, K. Pothula, J. Schroth, J. Satriano, H. Osswald, J. Schnermann, P. A. Insel, R. A. Bundey, and V. Vallon Vasopressin regulation of inner medullary collecting ducts and compensatory changes in mice lacking adenosine A1 receptors Am J Physiol Renal Physiol, March 1, 2008; 294(3): F638 - F644. [Abstract] [Full Text] [PDF]

				V. Vallon, C. Miracle, and S. Thomson Adenosine and kidney function: Potential implications in patients with heart failure Eur J Heart Fail, February 1, 2008; 10(2): 176 - 187. [Abstract] [Full Text] [PDF]

				V. Vallon P2 receptors in the regulation of renal transport mechanisms Am J Physiol Renal Physiol, January 1, 2008; 294(1): F10 - F27. [Abstract] [Full Text] [PDF]

				E. K. Jackson, J. Ren, L. C. Zacharia, and Z. Mi Characterization of Renal Ecto-Phosphodiesterase J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 810 - 815. [Abstract] [Full Text] [PDF]

				E. K. Jackson, Z. Mi, L. C. Zacharia, S. P. Tofovic, and R. K. Dubey The Pancreatohepatorenal cAMP-Adenosine Mechanism J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 799 - 809. [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]

				V. Vallon, B. Muhlbauer, and H. Osswald Adenosine and kidney function. Physiol Rev, July 1, 2006; 86(3): 901 - 940. [Abstract] [Full Text] [PDF]

				E. K. Jackson, L. C. Zacharia, M. Zhang, D. G. Gillespie, C. Zhu, and R. K. Dubey cAMP-Adenosine Pathway in the Proximal Tubule J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1219 - 1229. [Abstract] [Full Text] [PDF]

				T. Pawelczyk, M. Grden, R. Rzepko, M. Sakowicz, and A. Szutowicz Region-Specific Alterations of Adenosine Receptors Expression Level in Kidney of Diabetic Rat Am. J. Pathol., August 1, 2005; 167(2): 315 - 325. [Abstract] [Full Text] [PDF]