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)

In the present work we have been able to demonstrate the existence of some interrelationship between intracellular level of cAMP content and phenobarbital induction of delta-aminolevulinic acid synthase, ferrochelatase, and cytochrome P-450 biosynthesis in isolated rat hepatocytes. The increase of the level of intracellular cAMP produced by activators of adenylate cyclase, inhibitors of phosphodiesterase, or added cyclic nucleotides is reflected by an increase of the phenobarbital induction effect. The greater induction observed in hepatocytes of diabetic rats may be due to a higher level of the intracellular cAMP. The lack of potentiation of added cAMP in diabetic cells is mainly due to the fact that the maximum induction that could be attained is already achieved by the effect of the preexisting high level of the endogenous cAMP.
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PMID:Studies on regulatory mechanisms of heme biosynthesis in hepatocytes from normal and experimental-diabetic rats. Role of cAMP. 255 56

In the present work, we demonstrate the presence of a glucose inhibitory effect on the phenobarbital-mediated induction of the delta-aminolevulinate synthase mRNA in normal rat hepatocytes, consistent with the results obtained with the delta-aminolevulinate synthase activity previously reported. This "glucose effect" can be prevented by adding cAMP, adenylate cyclase activators, or a phosphodiesterase inhibitor. Delta-Aminolevulinate synthase mRNA half-life is not modified in the presence of phenobarbital or glucose. When the same experiments are performed using diabetic cells, no glucose effect is observed, even when the endogenous cAMP content is lowered to normal levels. The results obtained in this study suggest that glucose decreases delta-aminolevulinate synthase biosynthesis by acting at a pretranslational step. Assuming that the glucose effect operates by a repression mechanism exerted by metabolites derived from or related to glucose, the present results may reflect a derangement in the formation of these metabolites as a result of the abnormal metabolism operating in the diabetic state.
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PMID:Glucose inhibits phenobarbital-induced delta-aminolevulinate synthase expression in normal but not in diabetic rat hepatocytes. 921 37