Rolipram inhibited U937 cell phosphodiesterase-4 in either the presence or absence of saturating (100 micrograms/ml) phosphatidic acid in an apparently phospholipid-independent manner, exhibiting similar kinetics (Ki values = 0.41 and 0.59 microM, respectively). At low concentrations (10 and 100 nM), however, rolipram caused a rightward shift of the phosphatidic acid concentration-response curve for phosphodiesterase-4 activation, suppressing activation by up to 70%. Maximum inhibition of phosphodiesterase-4 activation occurred at phosphatidic acid concentrations of 5-40 micrograms/ml. The results suggest that rolipram is capable of inhibiting phosphodiesterase-4 by both phospholipid-dependent and phospholipid-independent mechanisms.
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