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Effects of solubilization and vanadate/glutathione complex on inhibitor potencies against eosinophil cyclic AMP‐specific phosphodiesterase
Author(s) -
Souness John E.,
Maslen Christopher,
Scott Lisa C.
Publication year - 1992
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(92)80435-j
Subject(s) - glutathione , chemistry , phosphodiesterase , rolipram , biochemistry , enzyme , vanadate , membrane
Treatment of membranes from guinea‐pig peritoneal eosinophils with deoxycholate and NaCl solubilized >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.