Faculty Collaboration Database

Cardioprotection following adenosine kinase inhibition in rat hearts. Basic Res Cardiol 2005 Jul;100(4):328-36

Date

03/30/2005

Pubmed ID

15795795

DOI

10.1007/s00395-005-0526-7

Scopus ID

2-s2.0-22144454977 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

Adenosine kinase phosphorylates adenosine to AMP, the primary pathway for adenosine metabolism under basal conditions. Inhibition of adenosine kinase results in a site-specific increase in interstitial adenosine. Using a rat model of myocardial infarction, we examined the protective effects of adenosine kinase inhibition. Male Sprague-Dawley rats underwent 30 min regional occlusion followed by 90 min reperfusion. Infarct size, expressed as a percent of the area-at-risk, IS/AAR(%), was 58.0 +/- 2.1 % in untreated rats. Pretreatment with the adenosine kinase inhibitor, 5-iodotubercidin (1 mg/kg), limited infarct development to 37.5+/-3.7% (P < 0.001). The A(1) adenosine receptor (A(1)AR) antagonist, DPCPX (100 microg/kg), abolished the infarct-sparing effect of 5-iodotubercidin (IS, 62.8 +/- 1.3%). Similarly, the A(3) adenosine receptor (A(3)AR) antagonist, MRS-1523 (2 mg/kg), and the delta-opioid receptor (DOR) antagonist, BNTX, (1 mg/kg) abolished the reduction of IS produced by iodotubercidin. Pretreatment with the ROS scavenger, 2-MPG (20 mg/kg), or the PKC-delta antagonist, rottlerin (0.3 mg/kg) also abolished iodotubercidin-mediated cardioprotection. Furthermore, pretreatment with 5-HD, a mitochondrial K(ATP) (mitoK(ATP)) channel inhibitor, but not the sarcolemmal K(ATP) channel blocker, HMR-1098, abrogated the beneficial effects of adenosine kinase inhibition (IS, 59.5 +/- 3.8%). These data suggest that inhibition of adenosine kinase is effective in reducing infarct development via A(1)AR, A(3)AR and DOR activation. Data also suggest that this protection is mediated via ROS, PKC-delta and mitoK(ATP) channels.

Author List

Peart JN, Gross GJ

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

Adenosine Kinase
Animals
Enzyme Inhibitors
Heart Rate
Male
Myocardial Infarction
Myocardial Ischemia
Potassium Channels
Protective Agents
Protein Kinase C
Protein Kinase C-delta
Rats
Rats, Sprague-Dawley
Reactive Oxygen Species
Receptors, G-Protein-Coupled
Signal Transduction