NDLI: The effect of glibenclamide on the production of interstitial adenosine by inhibiting ecto-5′-nucleotidase in rat hearts

Content Provider	PubMed Central
Author	Sato, Toshiaki Obata, Toshio Yamanaka, Yasumitsu Arita, Makoto
Copyright Year	1997
Abstract	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+ (KATP) channel antagonists (glibenclamide and 5-hydroxydecanoate) on the production of adenosine, by use of a flexibly mounted microdialysis technique. 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 μM (n=16). Introduction of AMP (100 μM) through the probe increased the dialysate adenosine markedly to 9.79±0.43 μM (n=12, P<0.001 vs baseline), and this increase was inhibited by the ecto-5′-nucleotidase inhibitor, α,β-methyleneadenosine 5′-diphosphate (100 μM), to 0.76±0.12 μM (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. Glibenclamide (0.1–100 μM) decreased the adenosine concentration measured during the perfusion of AMP (100 μM) in a concentration-dependent manner (IC50=10.5 μM). In contrast, 5-hydroxydecanoate (10–100 μM) did not affect the concentrations of dialysate adenosine, measured in the presence of AMP (100 μM). 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.
Related Links	http://dx.doi.org/10.1038/sj.bjp.0701424
Ending Page	618
Page Count	8
Starting Page	611
File Format	PDF
ISSN	00071188
Journal	British Journal of Pharmacology
Issue Number	4
Volume Number	122
Language	English
Publisher Date	1997-10-01
Access Restriction	Open
Subject Keyword	Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Pharmacology

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