Increased phosphorylation of DARPP-32 by D1 agonistic action of l-stepholidine in the 6-OHDA-lesioned rat striatum.
In order to explore the characteristics of l-stepholidine (SPD) activating the postsynaptic D(1) receptors, the effects of SPD on DARPP-32 phosphorylation in vivo with back-phosphorylation assay and on the postsynaptic D(1) receptor densities with radioligand assay were observed in the striatum of 6-OHDA-lesioned rat. The results showed that following subcutaneously administration of 20 or 40 mg/kg SPD for 21 d,  (32)P  phosphate incorporation into the DARPP-32 protein in the denervated striatum showed a 50% reduction (P<0.01) vs the intact striatum, indicating an increase of DARPP-32 phosphorylation in vivo in the denervated striatum. However,the D(1) receptor B(max) was decreased from 385.0+/-26.1 to 319.7+/-20.1 fmol/mg protein. It is suggested that D(1) agonist action of SPD decreases the D(1) receptor density but increases the phosphorylation of DARPP-32 in the striatum of 6-OHDA-lesioned rat, which may be responsible for the regulation of D(1) receptor signal transduction in brain neurons.
Liu
J
J
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 200031.
Guo
X
X
Wang
B C
BC
Jin
G Z
GZ
D000818:Animals; D001599:Berberine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D003342:Corpus Striatum / Q000378:metabolism / Q000503:physiopathology*; D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016627:Oxidopamine; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D015398:Signal Transduction
D018491:Dopamine Agonists; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017447:Receptors, Dopamine D1; D001599:Berberine; C010513:stepholidine; D016627:Oxidopamine