Methylxanthine effects on cyclic adenosine 3':5' monophosphate phosphodiesterase activity in preparations of neonatal rat cerebellum: modification by trifluoperazine

Paradoxically, caffeine was found to stimulate the activity of 3′:5′-cyclic AMP phosphodiesterase at substrate concentrations of 14μM, in cerebellar tissue from 10-day-old rats. Pretreatment with trifluoperazine, an inhibitor of calmodulin-dependent enzyme activation, converted the stimulatory effect of caffeine to the expected inhibitory action. Trifluoperazine pretreatment also increased the inhibitory action of theophylline on the cerebellar phosphodiesterase, but had no effect on the inhibitory action of 3-isobutyl-1-methylxanthine. It is suggested that caffeine and to a lesser extent theophylline in addition to their intrinsic phosphodiesterase inhibitory activity can also cause calmodulin dependent effects on cerebellar phosphodiesterase due to calcium mobilisation.