Oxidative stress inactivates ecto-5'-nucleotidase by inhibiting protein kinase C in rat hearts in vivo

Eur J Pharmacol. 2017 Jun 15;805:125-130. doi: 10.1016/j.ejphar.2017.02.019. Epub 2017 Feb 20.

Abstract

Examined in the present study, allopurinol are xanthine oxidase inhibitors for use in rat hearts in vivo dialysis technology and ventricular myocardial intersitial adenosine production can increase. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and the tissue in the vicinity of the dialysis was perfused with Tyrode's solution containing adenosine 5'-monophosphate (AMP) through the dialysis probe at a rate of 1.0ml/min to assess the activity of ecto-5'-nucleotidase. Allopurinol (10μM) significantly increased the level of adenosine in rat heart dialysate (n=6, p<0.05), which was inhibited by chelerythrine, 10μM, an antagonist of protein kinase C (PKC). Another free radical scavenger, coenzyme Q10 (CoQ10, 100μM) or ascorbic acid (Vitamin C; 100μM) also increased adenosine production. In addition, allopurinol enhanced the diacylglycerol (DAG; 50μM)-induced also increases in adenosine production by 71.5±12.0% (n=6, P<0.05), to a level significantly (P<0.05) greater than the increase caused by DAG alone (33.0±10.6%). In the presence of allopurinol (10μM), a marked elevation of AMP-primed dialysate adenosine in ischemia/reperfused rat hearts was observed. Free radical generation may suppress adenosine production via activation of PKC. The results suggest that oxidative stress may cause inactivation of nucleotidase, adenosine production in rat heart.

Keywords: Adenosine; Ecto-5'-nucleotidase; Microdialysis; Oxidative stress; Protein kinase C.

MeSH terms

  • 5'-Nucleotidase / metabolism*
  • Adenosine / pharmacology
  • Animals
  • Antigens, Plant / pharmacology
  • Enzyme Activation / drug effects
  • Male
  • Myocardial Reperfusion Injury / metabolism
  • Myocardium / metabolism*
  • Oxidative Stress* / drug effects
  • Plant Extracts / pharmacology
  • Protein Kinase C / antagonists & inhibitors*
  • Protein Kinase Inhibitors / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • Antigens, Plant
  • Plant Extracts
  • Protein Kinase Inhibitors
  • grass pollen extract, alum-adsorbed
  • Protein Kinase C
  • 5'-Nucleotidase
  • Adenosine