Effects of solubilization and vanadate/glutathione complex on inhibitor potencies against eosinophil cyclic AMP‐specific phosphodiesterase

FEBS Letters

Maslen, Christopher¹  Scott, Lisa C.¹  Souness, John E.¹ 

[1] Dagenham Research Centre, Rhône-Poulenc Rorer Limited, Rainham Road South, Dagenham, Essex, RM10 7XS, UK

关键词: Cyclic AMP;    Phosphodiesterase;    Eosinophil;    Inhibitor;   

DOI  :  10.1016/0014-5793(92)80435-J

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown