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Adenosine diphosphate ribose dilates bovine coronary small arteries through apyrase- and 5'-nucleotidase-mediated metabolism. J Vasc Res 2001 Jan-Feb;38(1):64-72

Date

02/15/2001

Pubmed ID

11173996

DOI

10.1159/000051031

Scopus ID

2-s2.0-0035105095   14 Citations

Abstract

Cyclic adenosine diphosphate ribose and adenosine diphosphate ribose (ADPR) play an important role in the regulation of intracellular Ca(2+) release and K(+) channel activity in the coronary arterial smooth muscle. The role of these signaling nucleotides in the control of vascular tone has yet to be determined. The present study was designed to determine whether ADPR produces vasodilation in coronary arteries and to explore the mechanism of action of ADPR. ADPR (10-60 micromol/l) was found to produce endothelium-independent relaxation in a concentration-dependent manner in isolated and pressurized small bovine coronary arteries. The ADPR-induced vasodilation was substantially attenuated by adenosine deaminase (0.2 U/ml), and the P(1) purinoceptor antagonist 8-(p-sulfophenyl)theophylline (50 micromol/l), with maximal inhibitions of 60 and 80%, respectively. When the coronary arterial homogenates were incubated with ADPR, the production of adenosine and 5'-AMP was detected. The adenosine production was blocked by the 5'-nucleotidase inhibitor, alpha,beta-methylene adenosine 5'-diphosphate (MADP, 1 mmol/l), which was accompanied by a corresponding accumulation of 5'-AMP. This 5'-AMP accumulation was substantially inhibited by the apyrase inhibitor sodium azide (10 mmol/l). Moreover, ADPR was hydrolyzed into 5'-AMP by purified apyrase. In agreement with their inhibitory effect on the adenosine production, MADP and sodium azide significantly attenuated the vasodilator response to ADPR. The metabolism of ADPR to adenosine was only detected in cultured coronary arterial smooth muscle cells but not in endothelial cells. We concluded that ADPR produces vasodilation in small coronary arteries and that the action of ADPR is associated with the adenosine production via an apyrase- and 5'-nucleotidase-mediated metabolism.

Author List

Zhang DX, Zou AP, Li PL

Author

David X. Zhang MD, PhD Associate Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

5'-Nucleotidase
Adenosine
Adenosine Deaminase
Adenosine Diphosphate
Adenosine Diphosphate Ribose
Adenosine Monophosphate
Animals
Apyrase
Cattle
Cells, Cultured
Coronary Vessels
Endothelium, Vascular
Enzyme Inhibitors
Muscle, Smooth, Vascular
Purinergic P1 Receptor Antagonists
Sodium Azide
Theophylline
Vasodilation
Vasodilator Agents
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a