Chronic treatment with (-)-stepholidine alters density and turnover of D1 and D2 receptors in striatum.
OBJECTIVE
To study the effects of chronic administration of SPD on the density and turnover of striatal D1 and D2 dopamine (DA) receptors.


METHODS
Receptor density was monitored by radio-receptor binding assay. The receptor recovery and turnover were studied after irreversible inactivation by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydro-quinoline (EEDQ).


RESULTS
Chronic SPD treatment (sc, 20 mg.kg-1.d-1 x 21 d) upregulated both striatal D1 and D2 receptor density. As compared to vehicle-treated rats, SPD increased D1 and D2 receptors by 41.5% and 43.7%, respectively SPD also altered the turnover of both D1 and D2 receptors. The degradation rate constant (k = 0.0082.h-1) and the synthesis rate (r = 2.65 pmol.h-1/g protein) of D2 receptors in SPD-treated rats were significantly increased vs vehicle-treated rats (k = 0.0049.h-1; r = 1.10 pmol.h-1/g protein). The degradation rate constant (k = 0.0059.h-1) and the synthesis rate (r = 3.1 pmol.h-1/g protein) of D1 receptors was also increased in SPD-treated rats vs vehicle-treated rats (k = 0.0048.h-1; r = 1.8 pmol.h-1/g protein), but the alteration of degradation rate constant missed significance (P > 0.05). As a result, receptor recovery following EEDQ was accelerated. The half time for D1 and D2 receptors recovery in SPD group were 117.5 h and 84.5 h, respectively, shorter than 144.4 h and 141.4 h in vehicle-treated rats.


CONCLUSIONS
Chronic SPD treatment upregulated D1 and D2 receptors, and accelerated DA receptor turnover and recovery mainly by increasing receptor synthesis.
Zou
L L
LL
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Cai
S T
ST
Jin
G Z
GZ
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001599:Berberine; C010513:stepholidine