Rolipram inhibition of phosphodiesterase-4 activation.
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.
DiSanto
M E
ME
Wyeth-Ayerst Research, Philadelphia, PA 19101, USA.
Heaslip
R J
RJ
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D001665:Binding Sites; D002460:Cell Line; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D006801:Humans; D010712:Phosphatidic Acids / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010743:Phospholipids / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D011760:Pyrrolidinones / Q000494:pharmacology*; D020889:Rolipram
D010712:Phosphatidic Acids; D010726:Phosphodiesterase Inhibitors; D010743:Phospholipids; D011760:Pyrrolidinones; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D020889:Rolipram