A role for soluble cAMP phosphodiesterases in differentiation of 3T3-L1 adipocytes.
Differentiation of 3T3-L1 adipocytes, monitored by accumulation of neutral lipid and by increase in alpha-glycerophosphate dehydrogenase activity, is accelerated by incubation of confluent 3T3-L1 fibroblasts in media containing insulin, dexamethasone and isobutylmethylxantine (IBMX). IBMX inhibits cyclic nucleotide phosphodiesterases as well as the binding of adenosine to its receptor. Agents with relatively specific effects were utilized to examine the role of IBMX in differentiation. Ro 20-1724, a selective inhibitor of soluble cAMP phosphodiesterase activities, was as effective as IBMX in increasing alpha-glycerophosphate dehydrogenase activity and fat deposition. Neither cilostamide, which inhibits particulate but not soluble cAMP phosphodiesterase activities, 8-phenyltheophylline, an adenosine receptor antagonist with little inhibitory effect on phosphodiesterase activities, nor N6-(R phenyl-isopropyl) adenosine (PIA), a potent adenosine receptor agonist, were effective in promoting differentiation. In addition, we find that maximal increases in alpha-glycerophosphate dehydrogenase activity and lipid accumulation were observed when differentiation was initiated in the presence of 10 nM dexamethasone. These data suggest that inhibition of soluble cAMP phosphodiesterase activity and subsequent alterations in cAMP may play an important role in the mechanism whereby IBMX enhances differentiation of 3T3-L1 cells.
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D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001391:Azo Compounds / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology; D050356:Lipid Metabolism; D051379:Mice; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D015363:Quinolones; D012995:Solubility; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
D001391:Azo Compounds; D007328:Insulin; D011804:Quinolines; D015363:Quinolones; D015124:8-Bromo Cyclic Adenosine Monophosphate; D010660:Phenylisopropyladenosine; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; C021294:cilostamide; D003907:Dexamethasone; D013806:Theophylline; C028322:8-phenyltheophylline; D005993:Glycerolphosphate Dehydrogenase; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D015106:3',5'-Cyclic-GMP Phosphodiesterases; C011049:oil red O; D015056:1-Methyl-3-isobutylxanthine