Effect of isoenzyme selective phosphodiesterase inhibitors on the proliferation of murine thymus and spleen cells.
The effects of isoenzyme selective phosphodiesterase inhibitors on mitogen-stimulated proliferation of murine thymus and spleen cells was determined. The type 4 phosphodiesterase inhibitors, (rolipram, RO 20-1724 and denbufylline) and the mixed type 3/4 inhibitors, (zardaverine and benzafentrine) produced a concentration-related inhibition of mitogen stimulated thymus and spleen cell proliferation. Combined addition of the type 4 inhibitor, rolipram and the type 3 inhibitor, SK&F 94836 had no antiproliferative effect additional to that of rolipram alone. The thymus cells were more sensitive to the type 4 inhibitors than the spleen cells. The type 3 phosphodiesterase inhibitor, SK&F 94836 significantly inhibited cell proliferation, but only at high concentrations. The type 1 (vinpocetine) and the type 5 (zaprinast) phosphodiesterase inhibitor had no significant effect on proliferation. These results suggest that thymus and to a lesser extent spleen cell proliferation is dependent on the activity of the type 4 phosphodiesterase isoenzyme.
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Department of Pharmacology, King's College London, UK.
Bertin
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Moodley
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D000818:Animals; D002455:Cell Division / Q000187:drug effects; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D020889:Rolipram; D013154:Spleen / Q000166:cytology / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects*
D006146:Guanidines; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D011760:Pyrrolidinones; C056215:siguazodan; D020889:Rolipram; C066436:zardaverine