Nicorandil increases adenosine 5'-monophosphate-primed interstitial adenosine via activation of ecto-5'-nucleotidase in rat hearts.
With the use of microdialysis techniques, we examined the effects of nicorandil, a hybrid of an ATP-sensitive K+ (K ATP) channel opener and a nitrate compound, on the production of interstitial adenosine in rat hearts in situ. The level of dialysate adenosine measured under a constant supply of adenosine 5'-monophosphate (AMP) reflected the activity of endogenous ecto-5'-nucleotidase. Nicorandil (0.3-3mM) increased the level of AMP (100 microM)-primed dialysate adenosine in a concentration-dependent manner, and this effect was completely abolished by the guanylate cyclase inhibitor, methylene blue (100 microM), but not by the K ATP channel blocker, glibenclamide (10 microM). Another K ATP channel opener, cromakalim (0.1-1mM), did not increase the production of AMP-primed dialysate adenosine. These results suggest that nicorandil increases the level of interstitial adenosine via cyclic guanosine monophosphate-mediated activation of ecto-5'-nucleotidase.
Sato
T
T
Department of Physiology, Oita Medical University, Hasama, Japan. tsato@oita-med.ac.jp
Obata
T
T
Yamanaka
Y
Y
Arita
M
M
D015720:5'-Nucleotidase / Q000378:metabolism*; D000241:Adenosine / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000818:Animals; D005260:Female; D006321:Heart / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D020108:Nicorandil; D000249:Adenosine Monophosphate; D015720:5'-Nucleotidase; D000241:Adenosine