doi: 10.1161/01.RES.0000146278.94064.4b
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© 2004 American Heart Association, Inc.
Editorials |
Cardiovascular Ecto-5'-Nucleotidase
An End to 40 Years in the Wilderness?
From the Suncoast-AHA Cardiovascular Research Laboratory, Departments of Internal Medicine and Pharmacology and Therapeutics, University of South Florida, Tampa, Fla.
Correspondence to Ray A. Olsson, Department of Internal Medicine, MDC Box 19, 12901 Bruce B. Downs Blvd, Tampa, FL 33612. E-mail rolsson@hsc.usf.edu
See related article, pages 814–821
Key Words: adenosine • CD 73 • cell adhesion molecules • coronary flow • ecto-phosphatases • inflammation
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Elsewhere in this issue, Koszalka et al1 add another chapter to the long-running saga of the significance of ecto-5'-nucleotidase (CD-73) in cardiovascular function, showing that this enzyme catalyzes the formation of adenosine in amounts sufficient to have important physiological effects. A brief sketch of the tortuous path to our present understanding of the role of this enzyme puts this work in perspective. It also illustrates how science evolves stepwise, testing hypotheses based on available evidence and modifying them to fit the new evidence. In the early 1960s, Berne2 and, independently, Gerlach et al3 showed that hypoxia stimulated adenosine production in the heart. Within a few years, histochemists showed phosphatase activity able to hydrolyze AMP on the surface of cardiac and skeletal muscle myocytes. At first this seemed to provide an explanation for the adenosine released from hypoxic heart muscle, but there was a serious problem. The enzyme was outside the cell, but its substrate, AMP, was in the cytoplasm, separated by a sarcolemma thought at the time to be impermeable to nucleotides. Theories advanced to resolve this dilemma included the idea that the ectoenzyme also had transport capacity, but this faltered for lack of direct evidence. There was little further progress for approximately a decade, in part because the discovery of nitric oxide-mediated vasodilation4 dispelled the notion that adenosine was "the" regulator of coronary vascular resistance. Then, Japanese and American workers isolated cytosolic nucleotidases, and Andrew Newby clinched the importance of the cytosolic enzyme by showing that leukocytes
Related Article:
Circ. Res. 2004 95: 814-821.