Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.3.5 (5'-nucleotidase)
 3,167 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that the opening of ATP-sensitive K+ channels contributes to activation of ectosolic 5'-nucleotidase and the infarct size-limiting effect of ischemic preconditioning. In open-chest dogs, the left anterior descending coronary artery was occluded four times for 5 min each, separated by a 5-min period of reperfusion (ischemic preconditioning, n = 8). After this procedure, the coronary artery was occluded for 90 min, followed by 6 h of reperfusion. Infarct size was smaller in this group than in the group (control, n = 8) with a 45 min interval instead of the ischemic preconditioning procedure (40.1 +/- 3.9 vs. 6.4 +/- 1.9%). Glibenclamide blunted the infarct size-limiting effect of ischemic preconditioning (infarct size, 37.3 +/- 5.8%; n = 7), and transient exposures to cromakalim and nicorandil mimicked it [infarct size, 10.1 +/- 3.1 (n = 7) and 11.1 +/- 2.7% (n = 8), respectively]. Ectosolic and cytosolic 5'-nucleotidase activity increased in the ischemic preconditioning group compared with that in the control group; this preconditioning-induced increase in 5'-nucleotidase activity was blunted by glibenclamide (n = 5) and mimicked by cromakalim (n = 5) and nicorandil (n = 5). The infarct size-limiting effect due to cromakalim and nicorandil was blunted by alpha,beta-methyleneadenosine 5'-diphosphate, an inhibitor of ectosolic 5'-nucleotidase [infarct size, 37.7 +/- 5.6 (n = 9) and 36.8 +/- 4.8% (n = 7), respectively] and 8-sulfophenyltheophylline (infarct size with cromakalim, 44.7 +/- 4.6%; n = 7). We conclude that activation of ectosolic 5'-nucleotidase due to the openers of ATP-sensitive K+ channels contributes to the infarct size- limiting effect of ischemic preconditioning.
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PMID:Role of activation of ectosolic 5'-nucleotidase in the cardioprotection mediated by opening of K+c channels. 892 82

1. Adenosine exerts cardioprotective effects on the ischaemic myocardium. The production of adenosine in the ischaemic myocardium is attributed primarily to the enzymatic dephosphorylation of adenosine 5'-monophosphate (AMP) by 5'-nucleotidase. We determined the activity of 5'-nucleotidase in rat hearts. The objective of the study was to determine the effects of ATP-sensitive K+ (K[ATP]) channel antagonists (glibenclamide and 5-hydroxydecanoate) on the production of adenosine, by use of a flexibly mounted microdialysis technique. 2. Rats were anaesthetized and the microdialysis probe was implanted in the left ventricular myocardium, followed by perfusion with Tyrode solution. The baseline level of dialysate adenosine was 0.51 +/- 0.09 microM (n = 16). Introduction of AMP (100 microM) through the probe increased the dialysate adenosine markedly to 9.79 +/- 0.43 microM (n = 12, P < 0.001 vs baseline), and this increase was inhibited by the ecto-5'-nucleotidase inhibitor, alpha,beta-methyleneadenosine 5'-diphosphate (100 microM), to 0.76 +/- 0.12 microM (n = 8). Thus, the dialysate adenosine noted during the perfusion of AMP originated from dephosphorylation of AMP by ecto-5'-nucleotidase, and the dialysate level of adenosine attained reflects the ecto-5'-nucleotidase activity in the tissue in situ. 3. Glibenclamide (0.1-100 microM) decreased the adenosine concentration measured during the perfusion of AMP (100 microM) in a concentration-dependent manner (IC50 = 10.5 microM). In contrast, 5-hydroxydecanoate (10-100 microM) did not affect the concentrations of dialysate adenosine, measured in the presence of AMP (100 microM). These results suggest that glibenclamide inhibits the activity of endogenous ecto-5'-nucleotidase and decreases the concentration of adenosine in the interstitial space of rat ventricular muscles in situ.
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PMID:The effect of glibenclamide on the production of interstitial adenosine by inhibiting ecto-5'-nucleotidase in rat hearts. 937 55