Changes in soluble calmodulin following activation of dopamine receptors in rat striatal slices.

Various molecular forms of cyclic nucleotide phosphodiesterase (PDE) are present in the striatum of rats. While Ca²⁺ by itself cannot modulate striatal PDE, this ion is essential for the activation of striatal PDE by calmodulin (CaM). Incubation of striatal slices with apomorphine (10^?7 M) for 30 min increased the total CaM content of the supernatant fraction. Also the amount of CaM associated with PDE was increased and the K_m of PDE for cAMP was lowered. A shorter incubation with dopamine or apomorphine (10 min) failed to increase CaM and to lower the K_m of PDE.Haloperidol (10^?7 M), a dopamine receptor antagonist, prevented the change in the kinetic profile of PDE elicited by dopamine (2 × 10^?7M). Transection of the nigra-striatal fibre bundle by itself did not change the kinetic profile of striatal PDE, but in slices prepared from deafferented striata, a 30 min activation of dopamine receptors still elicited a decrease in the K_m of PDE for cAMP. These findings suggest that following a persistent stimulation of dopamine receptors, the CaM content increases in the cytosol because it is mobilized from a pool located in post-synaptic membranes. This mobilization of CaM regulates PDE; thus, regulation of PDE through a translocation of CaM may participate in reducing the functional output of dopamine receptors following persistent stimulation.