Stimulation of glycogenolysis in isolated hepatocytes by adenosine and one of its analogues is inhibited by caffeine.
The adenosine analogues 5'-(N-ethyl)carboxamidoadenosine (NECA) and N6-(phenylisopropyl)adenosine (PIA) activate glycogen phosphorylase 5-fold and 4.2-fold respectively in rat hepatocytes incubated in the absence of endogenous adenosine. Half-maximally effective concentrations are 0.5 microM for NECA and 20 microM for PIA, demonstrating the presence of A2-adenosine receptors. Exogenous adenosine activates phosphorylase 4.6-fold, but high rates of adenosine disappearance from the medium render estimates of its half-maximally effective concentration unreliable. These effects of NECA and adenosine are inhibited by 0.1 mM-caffeine. Activation of phosphorylase by a physiological concentration of adenosine (3.3 microM) was 50% inhibited by a physiological concentration of caffeine (35 microM).
Stanley
J C
JC
Nestlé Research Centre, Nestec Ltd., Lausanne, Switzerland.
Markovic
J
J
Gutknecht
A M
AM
Lozeman
F J
FJ
D000241:Adenosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000243:Adenosine Deaminase / Q000494:pharmacology; D019830:Adenosine-5'-(N-ethylcarboxamide); D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002469:Cell Separation; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D006005:Phosphorylases / Q000037:antagonists & inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical
D008112:Liver Glycogen; D010660:Phenylisopropyladenosine; D019830:Adenosine-5'-(N-ethylcarboxamide); D002110:Caffeine; D005934:Glucagon; D006005:Phosphorylases; D000243:Adenosine Deaminase; D000241:Adenosine