Regulation of hepatocyte cAMP and pyruvate kinase by site-specific analogs of adenosine.
The effects of site-specific analogs of adenosine on cAMP content and pyruvate kinase activity of isolated rat hepatocytes were studied. N6-(phenylisopropyl) adenosine (PIA), a metabolically stable analog of adenosine which acts specifically at 'R' sites, increased cAMP content and decreased pyruvate kinase activity to about the same extent as did epinephrine, By contrast, adenosine itself was without effect. Consistent with 'R'-site mediated effects, the effects of PIA were blocked by 3-isobutyl-l-methylxanthine. 2'5'-Dideoxyadenosine, which acts specifically at 'p' sites to inhibit adenylate cyclase, counteracted the effects of epinephrine on pyruvate kinase, but paradoxically not the effects of PIA. The adenylate cyclase in membranes from these parenchymal cells was determined and was found to exhibit comparable sensitivity to 'R' site-specific analogs and other activators as did the enzyme prepared from whole liver. Thus, the data suggest that the effects on liver metabolism of 'R' site-specific analogs of adenosine are initiated by an adenosine-receptor coupled activation of adenylate cyclase and that these effects are characteristics of the parenchymal cells.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000241:Adenosine / Q000031:analogs & derivatives*; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D003839:Deoxyadenosines / Q000031:analogs & derivatives / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D004837:Epinephrine / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011770:Pyruvate Kinase / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D003839:Deoxyadenosines; D010660:Phenylisopropyladenosine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D011770:Pyruvate Kinase; D000262:Adenylyl Cyclases; D000241:Adenosine; D015056:1-Methyl-3-isobutylxanthine; D004837:Epinephrine