(-)-Stepholidine antagonizes the inhibition by D2 receptor agonists on synaptosomal tyrosine hydroylase in rat corpus striatum
Abstract
AIM:
To evaluate the action of (-)-stepholidine (SPD), a novel dopamine (DA) receptor antagonist, on inhibition by presynaptic D2 receptor agonists on the activity of synaptosomal tyrosine hydroxylase (TH) in the striatum.
METHOD:
The TH activity was measured by HPLC-ECD.
RESULTS:
The mixed DA receptor agonist apomorphine (Apo 10.4 nmol L-1) and selective D2 receptor agonists N-0437 (0.4 pmol L-1) and quinpirole (0.8 mumol L-1) inhibited the activity of TH, while selective D1 receptor agonist SKF 38393 (0.001-10 mumol L-1) and SPD (1-100 mumol L-1) failed to inhibit the TH activity. The inhibition of N-0437 and quinpirole were antagonized by D2 receptor antagonist spiperone and SPD.
CONCLUSION:
The negative feedback regulation of presynaptic DA receptors is mediated via D2 receptors and SPD is an antagonist on presynaptic D2 DA receptors.
Keywords:
To evaluate the action of (-)-stepholidine (SPD), a novel dopamine (DA) receptor antagonist, on inhibition by presynaptic D2 receptor agonists on the activity of synaptosomal tyrosine hydroxylase (TH) in the striatum.
METHOD:
The TH activity was measured by HPLC-ECD.
RESULTS:
The mixed DA receptor agonist apomorphine (Apo 10.4 nmol L-1) and selective D2 receptor agonists N-0437 (0.4 pmol L-1) and quinpirole (0.8 mumol L-1) inhibited the activity of TH, while selective D1 receptor agonist SKF 38393 (0.001-10 mumol L-1) and SPD (1-100 mumol L-1) failed to inhibit the TH activity. The inhibition of N-0437 and quinpirole were antagonized by D2 receptor antagonist spiperone and SPD.
CONCLUSION:
The negative feedback regulation of presynaptic DA receptors is mediated via D2 receptors and SPD is an antagonist on presynaptic D2 DA receptors.