title: Effects of solubilization and vanadate/glutathione complex on inhibitor potencies against eosinophil cyclic AMP-specific phosphodiesterase.
abstract: Treatment of membranes from guinea-pig peritoneal eosinophils with deoxycholate and NaCl solubilized greater than 95% of the particulate cyclic AMP-specific phosphodiesterase (PDE IV). Solubilized PDE IV was at least 10 times more potently inhibited by selective PDE IV inhibitors (e.g. rolipram, denbufylline) than bound enzyme. Vanadate/glutathione complex (V/GSH) activated membrane-bound PDE IV and also increased potencies of these same inhibitors by at least 10-fold. Neither solubilization nor V/GSH markedly influenced the inhibitory activities of non-selective inhibitors (e.g. trequinsin, dipyridamole). Inhibitor effects on solubilized PDE IV and cyclic AMP accumulation in intact cells were strongly correlated. These results suggest a biologically important site on eosinophil PDE IV which is concealed or partially concealed in freshly prepared membranes and is exposed by solubilization or V/GSH.
authors.affiliation: Dagenham Research Centre, Rhône-Poulenc Rorer Limited, Dagenham, Essex, UK.
authors.forename: J E
authors.initials: JE
authors.lastname: Souness
authors.forename: C
authors.initials: C
authors.lastname: Maslen
authors.forename: L C
authors.initials: LC
authors.lastname: Scott
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D004804:Eosinophils / Q000201:enzymology*; D005978:Glutathione / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D012995:Solubility; D014638:Vanadates / Q000378:metabolism* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
chemical_list: D011760:Pyrrolidinones; D014970:Xanthines; C043898:denbufylline; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D014638:Vanadates; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D005978:Glutathione; D020889:Rolipram