Blockade by haloperidol of the increase in tryptophan hydroxylase activity induced by incubation of slices of brain stem with dibutyryl cyclic AMP

Abstract

Pretreatment of rat brain stem slices with dibutyryl cyclic AMP, caffeine, theophylline and 3-isobutyl-1-methylxanthine increased the activity of tryptophan hydroxylase in supernatant preparations of enzyme made from the slices. This effect does not appear to be mediated by a cyclic AMP sensitive mechanism since it was not reproduced by exposure of the slices to 8-bromo cyclic AMP, to papaverine, a nonxanthine phosphodiesterase inhibitor, or to other treatments known to raise tissue cyclic AMP levels. The ability of haloperidol to block this increase in enzyme activity is consistent with a role for calmodulin and calcium as mediators of the enzyme activation, particularly when this observation is considered in conjunction with the evidence that supernatant preparations of this enzyme was activated under phosphorylating conditions by a calcium-calmodulin dependent process [5]. Nevertheless, in view of the high concentrations of haloperidol employed in the present experiments, the possibility that this drug may produce its effects in the brain stem slices through some other action, unrelated to its ability to bind to calmodulin, should be kept in mind.