Effect of chlorpropamide and phenformin on rat liver: the effect on plasma membrane-bound enzymes and cyclic AMP content of hepatocytes in vitro.
Chlorpropamide and phenformin inhibited (Na+ - K+)-ATPase and stimulated a high affinity cyclic AMP-phosphodiesterase of isolated liver plasma membrane when tested in vitro. In addition, the two drugs decreased the intracellular cyclic AMP content of isolated hepatocytes without being effective on plasma membrane-bound adenylate cyclase. The results suggest that the plasma membrane plays an important role in the mechanism of action of the two hypoglycemic drugs, but do not exclude the presence of intracellular targets.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002747:Chlorpropamide / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D005260:Female; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D010101:Oxygen Consumption / Q000187:drug effects; D010629:Phenformin / Q000494:pharmacology*; D051381:Rats
D007328:Insulin; D000255:Adenosine Triphosphate; D010629:Phenformin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000251:Adenosine Triphosphatases; D000262:Adenylyl Cyclases; D002747:Chlorpropamide