Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Effect of chlorpropamide and phenformin on rat liver: the effect on plasma membrane-bound enzymes and cyclic AMP content of hepatocytes in vitro. 20 70

The effect of chlorpropamide was determined in Brattleboro diabetes insipidus (DI) rats that were injected with 1-deamino-8-D-arginine vasopressin (dDAVP). Chlorpropamide augmented the antidiuretic responses to 0.78 and 1.56 ng dDAVP but not to larger doses. In an effort to explain this observation we investigated the effect of chlorpropamide on renal medullary adenylate cyclase activation by dDAVP and on phosphodiesterase activity. We found that the injection of chlorpropamide increased adenylate cyclase activation by dDAVP added in vitro to renal medullary cell membrane preparations from Brattleboro DI rats but had no effect on phosphodiesterase activity. When kidneys from Brattleboro DI rats, treated and not treated with chlorpropamide, were perfused in vitro, we found that 10(-4) M dDAVP increased the concentration of cAMP in comparison to untreated and chlorpropamide-treated groups, and that chlorpropamide plus dDAVP resulted in a greater concentration of renal cAMP than was found with dDAVP alone. We believe that treatment with chlorpropamide increases dDAVP-stimulated renal medullary adenylate cyclase activity without altering phosphodiesterase activity and that this leads to increased renal cAMP concentrations. This, in turn, causes an augmented antidiuresis in response to dDAVP.
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PMID:Augmentation by chlorpropamide of 1-deamino-8-D-arginine vasopressin-induced antidiuresis and stimulation of renal medullary adenylate cyclase and accumulation of adenosine 3',5'-monophosphate. 624 58