title: Chronic treatment with (-)-stepholidine alters density and turnover of D1 and D2 receptors in striatum.
abstract: 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.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Zou
authors.forename: S T
authors.initials: ST
authors.lastname: Cai
authors.forename: G Z
authors.initials: GZ
authors.lastname: Jin
mesh_terms: 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*
chemical_list: D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001599:Berberine; C010513:stepholidine