8'-aminoguanosine inclusion results in enhanced efflux of taurine in preconditioned ischemic myocardium.
Attenuated purine levels are characteristic findings of ischemic preconditioning (PC). Lower energy demand in PC myocardium leading to less nucleotide decay is a reasonable explanation. However, experimental data suggest that the activities of the enzymes involved in purine metabolism are increased in PC myocardium. Recently it was suggested that PC favored degradation of exogenous adenosine to inosine successively ending up in enhanced lactate production. This was probably because of the involvement of the hexose monophosphate pathway in the PC ischemic myocardium. This route may therefore be supplementary in energy metabolism as a metabolic flow can be started by adenosine ending up in lactate without initial adenosine 5'-triphosphate (ATP) investment. Purine nucleoside phosphorylase (PNP) is a key enzyme in the proposed metabolic route. In the current study the effect of PNP inhibition (with 8'-aminoguanosine) on myocardial energy metabolism during PC was studied in an open chest porcine heart model using the microdialysis technique. A dose-dependent inhibition of PNP by 8'-aminoguanosine was observed in PC myocardium. This inhibition resulted in an enhanced exodus of taurine reflecting a disturbed energy economy of the cardiomyocytes. Addition of inosine being a true substrate of PNP reversed these changes, which indicated that 8'-aminoguanosine was a competitive inhibitor of PNP. It is concluded that the ischemic PC phenomenon at least partly involves the activated enzyme PNP.
Kavianipour
Mohammad
M
Department of Cardiology, Norrland University Hospital, Umeå, Sweden.
Ronquist
Gunnar
G
Wikström
Gerhard
G
Waldenström
Anders
A
D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors; D013552:Swine; D013654:Taurine / Q000378:metabolism*
C402368:N(7)-aminoguanosine; D006151:Guanosine; D013654:Taurine; D011683:Purine-Nucleoside Phosphorylase