Augmentation of dopamine release by (-)-stepholidine from rabbit and rat caudate slices
Abstract
AIM:
To study the effect of (-)-stepholidine (SPD) on dopamine (DA) release evoked by electric stimulation on slices of rabbit caudate nucleus.
METHODS:
Slices of rabbit caudate nucleus were preincubated with [3H]DA and then perfused and stimulated electrically.
RESULTS:
Quinpirole (Qui), a selective DA D2 receptor agonist, reduced [3H]DA overflow elicited by 24 mA electric stimulation (IC50 = 0.12, 95% confidence limits 0.09-0.17 mumol . L-1). SPD markedly increased the potential of the stimulation-evoked [3H]DA overflow in a dose-dependent manner and reversed Qui (1 mumol . L-1)-induced attenuation of [3H]DA release. The pA2 value calculated from the data of [3H]DA overflow for SPD was 7.495. In the experiments with rat caudate nucleus slices, SPD (0.1 mmol . L-1) increased the [3H]DA outflow from 3.3 +/- 0.2% to 6.5 +/- 0.5% of the tissue [3H]DA content, which was further enhanced by the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDB, 1 mumol . L-1) to 10.1 +/- 1.0% of the total [3H]DA in the tissue.
CONCLUSION:
SPD is a presynaptic D2 autoreceptor antagonist and induces a synergic effect on [3H]DA release process with PKC.
Keywords:
To study the effect of (-)-stepholidine (SPD) on dopamine (DA) release evoked by electric stimulation on slices of rabbit caudate nucleus.
METHODS:
Slices of rabbit caudate nucleus were preincubated with [3H]DA and then perfused and stimulated electrically.
RESULTS:
Quinpirole (Qui), a selective DA D2 receptor agonist, reduced [3H]DA overflow elicited by 24 mA electric stimulation (IC50 = 0.12, 95% confidence limits 0.09-0.17 mumol . L-1). SPD markedly increased the potential of the stimulation-evoked [3H]DA overflow in a dose-dependent manner and reversed Qui (1 mumol . L-1)-induced attenuation of [3H]DA release. The pA2 value calculated from the data of [3H]DA overflow for SPD was 7.495. In the experiments with rat caudate nucleus slices, SPD (0.1 mmol . L-1) increased the [3H]DA outflow from 3.3 +/- 0.2% to 6.5 +/- 0.5% of the tissue [3H]DA content, which was further enhanced by the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDB, 1 mumol . L-1) to 10.1 +/- 1.0% of the total [3H]DA in the tissue.
CONCLUSION:
SPD is a presynaptic D2 autoreceptor antagonist and induces a synergic effect on [3H]DA release process with PKC.