ACTH-(1-24) enhances the electrically stimulated release of [3H]dopamine from rat septal slices via a dopamine D2 receptor-independent mechanism.

ACTH-(1-24) enhanced the basal as well as the electrically stimulated release of [3H]dopamine from rat septal slices in vitro. In the absence of Ca2+ from the superfusion medium the effect of ACTH-(1-24) on the electrically stimulated release of [3H]dopamine was abolished. The stimulus-evoked release of [3H]dopamine from septal slices appeared to be modulated through dopamine receptors of the D2 subtype: the dopamine D2 receptor agonists 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) and quinpirole reduced, whereas the dopamine D2 receptor antagonist sulpiride enhanced the electrically stimulated release of [3H]dopamine. The magnitude of the effect of ACTH-(1-24) on [3H]dopamine release was the same in the presence or absence of N-0437, quinpirole and sulpiride. ACTH-(1-24) had no effect on either the basal or the electrically stimulated release of [3H]noradrenaline. Also when the electrically stimulated release of [3H]noradrenaline was reduced by the alpha 2-adrenoceptor agonist clonidine, the peptide was without effect. These results show that ACTH-(1-24) selectively enhances the release of [3H]dopamine from septal slices. The effect of the peptide is independent of the degree of activation of dopamine D2 receptors which modulate the stimulus-evoked release of [3H]dopamine. These results suggest that ACTH-(1-24) enhances the stimulus-evoked release of dopamine in the septum via a mechanism not associated with dopamine D2 autoreceptors.