This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wagner, D. R. Articles by van den Berghe, G. Search for Related Content PubMed PubMed Citation Articles by Wagner, D. R. Articles by van den Berghe, G.

Circulation, Vol 90, 1343-1349, Copyright © 1994 by American Heart Association

ARTICLES

Existence and role of substrate cycling between AMP and adenosine in isolated rabbit cardiomyocytes under control conditions and in ATP depletion

DR Wagner, F Bontemps and G van den Berghe
Laboratory of Physiological Chemistry, International Institute of Cellular and Molecular Pathology, Brussels, Belgium.

BACKGROUND: Adenosine, a physiological coronary vasodilator, has been proposed to regulate coronary circulation according to myocardial oxygen demand. In the present study, we investigated the mechanisms of adenosine formation and utilization in isolated rabbit cardiomyocytes and, in particular, the existence and the role of substrate cycling between AMP and adenosine in the regulation of its concentration. METHODS AND RESULTS: Rabbit cardiomyocytes were isolated by collagenase perfusion and incubated in HEPES-buffered Krebs-Henseleit solution at 37 degrees C, pH 7.4, in control conditions and in ATP depletion achieved by inhibiting glycolysis with 5 mmol/L iodoacetate. Under control conditions, adenosine accumulated at a rate of 4 pmol.min-1.10(- 6) cells. The 13-fold elevation of adenosine accumulation induced by iodotubercidin (ITu), an inhibitor of adenosine kinase, proves that adenosine is normally recycled into AMP. This recycling involves 95% of the adenosine formed. In ATP depletion, adenosine accumulated at the rate of 335 pmol.min-1.10(-6) cells and was no longer rephosphorylated after 20 minutes, as shown by the absence of effect of ITu after this time interval. Moreover, adenosine was deaminated, as indicated by the twofold increase of its accumulation induced by deoxycoformycin (dCF), an inhibitor of adenosine deaminase. Both in control conditions and in ATP depletion, adenosine-dialdehyde, an inhibitor of S- adenosylhomocysteine (SAH) hydrolase, had no significant effect on adenosine formation, indicating that the transmethylation pathway is not an important source of adenosine in rabbit cardiomyocytes. CONCLUSIONS: The results indicate that recycling of adenosine into AMP is essential for the maintenance of low, nonvasodilatory concentrations of the nucleoside under control conditions and that interruption of recycling plays an important role in elevating adenosine during ATP depletion.

This article has been cited by other articles:

				T. H. Adair Growth regulation of the vascular system: an emerging role for adenosine Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2005; 289(2): R283 - R296. [Abstract] [Full Text] [PDF]

				Y. Chen, S. Epperson, L. Makhsudova, B. Ito, J. Suarez, W. Dillmann, and F. Villarreal Functional effects of enhancing or silencing adenosine A2b receptors in cardiac fibroblasts Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2478 - H2486. [Abstract] [Full Text] [PDF]

				J. P. Headrick, B. Hack, and K. J. Ashton Acute adenosinergic cardioprotection in ischemic-reperfused hearts Am J Physiol Heart Circ Physiol, November 1, 2003; 285(5): H1797 - H1818. [Abstract] [Full Text] [PDF]

				R. T. Smolenski, O. Raisky, E. M. Slominska, H. Abunasra, K. K. Kalsi, J. Jayakumar, K. Suzuki, and M. H. Yacoub Protection From Reperfusion Injury After Cardiac Transplantation by Inhibition of Adenosine Metabolism and Nucleotide Precursor Supply Circulation, September 18, 2001; 104 (2009): I-246 - I-252. [Abstract] [Full Text] [PDF]

				D. R. Wagner, A. Combes, C. McTiernan, V. J. Sanders, B. Lemster, and A. M. Feldman Adenosine Inhibits Lipopolysaccharide-Induced Cardiac Expression of Tumor Necrosis Factor-{alpha} Circ. Res., January 23, 1998; 82(1): 47 - 56. [Abstract] [Full Text] [PDF]

				S. A Manthei, C. M Reiling, and D. G.L Van Wylen Dual cardiac microdialysis to assess drug-induced changes in interstitial purine metabolites: adenosine deaminase inhibition versus adenosine kinase inhibition Cardiovasc Res, January 1, 1998; 37(1): 171 - 178. [Abstract] [Full Text] [PDF]

				U. K. M. Decking, G. Schlieper, K. Kroll, and J. Schrader Hypoxia-Induced Inhibition of Adenosine Kinase Potentiates Cardiac Adenosine Release Circ. Res., August 19, 1997; 81(2): 154 - 164. [Abstract] [Full Text]