Parkinsons disease(PD) is characterized by a selective lo ss of dopaminergic neurons in the substantia nigra pars compacta. The etiology of PD is still not full y understood. Molecular pathways such as oxidative stress, mitochondrial dysfunc tion and impairment in the ubiquitinproteasomal system, are involved in the proc ess of the dopaminergic neuronal cell death and the progress of PD. The explorat ion and elucidation of these molecular pathways will provide new potential targe ts for the drug therapy of PD.

G-protein-coupled receptors (GPCRs) are major targets for drug discovery. The regulator of G-protein signaling (RGS) proteins is a recently identified protein family,which strongly modulates the activity of G proteins. RGS proteins accelerate the deactivation of G proteins to reduce GPCR signaling; however, some also have an effector function and transmit signals. Combining GPCR agonists with RGS inhibitors should potentiate responses and markedly increase the regional specificity of agonist. In the central nervous system, RGS proteins have unique tissue distributions and are strongly regulated by signal transduction events. Thus the diversity of RGS makes them attractive targets for pharmacotherapy of neurological disorders.

Objective To study the effects of ketamine on glutamate-induced apoptosis in neuronal cells using PC 12 pheochromocytoma cell line (provided by Chinese Academy of Phamacological Research) .Methods After being incubated in the culture medium containing 7S-NGF for 6 days. Over 95 % of the PC cells differentiated into neuron-type cells. The 7S-NGF induced differentiated neuronal PC 12 cells were seeded in 24-well plates pre-coated with poly-L-lysine(2?106 cells per well) .24 hours later the PC12 cells were exposed to glutamate 20 mrnol/ L(group A); glutamate 20 mmol/L + ketamine 0.1 mmo/L (group B); glutamate 20 mmol/L + ketamine 1.0 mmol/L (group C); glutamate 20 mmol/L + D-APS 100 )Ltmol/L(group D) and new culture medium containing no 7S-NGF(group E, control group), and incubated for 18 hours .The viability of the cells was evaluated by the ability of the cells to reduce the tetragotium derivative MTT into a blue formagan salt. DNA fragmentation indicative of apoptosis was detected using TUNEL technique. Results in group A following incubation with glutamate 20 mmol/L for 18 h , at 37℃, the viability was PC 12 cells was reduced to 37%? 6% However ketamine , when added to the culture medium to gather with glutamate , inhibited glutamate-induced cell death . The viability of PC 12 cell was 65 ? 7% in group B an 99?10% in group C. Ketamine appeared to attenuate the apoptotic process, because the number of the apoptotic cell bodies, determinated by YUNEL was also reduced by ketamine, with only 15-20% of neuronal cells staining positive after exposure to 20 mmol/L glutamate.The difference between group A and C was very significant (P