(-)-Stepholidine antagonizes the inhibition by D2 receptor agonists on synaptosomal tyrosine hydroylase in rat corpus striatum.
OBJECTIVE
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.


METHODS
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.


CONCLUSIONS
The negative feedback regulation of presynaptic DA receptors is mediated via D2 receptors and SPD is an antagonist on presynaptic D2 DA receptors.
Hu
G
G
Shanghai Institute of Materia Medica, Chinese Academy of Sciences.
Jin
G Z
GZ
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013574:Synaptosomes / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects* / Q000378:metabolism
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D001599:Berberine; C010513:stepholidine; D014446:Tyrosine 3-Monooxygenase