Individual and combined effects of rhynchophylline and ketamine on proliferation, NMDAR1 and GluA2/3 protein expression in PC12 cells.
Rhynchophylline is an active component of the Uncaria species, which is a member of the Rubiaceae family. Our studies show that the downregulation of N-methyl-d-aspartate (NMDA) receptor subunit GluN2B expression in the nucleus accumbens, amygdala, medial prefrontal cortex, and hippocampal CA1 area by rhynchophylline is beneficial for the treatment of psychological dependence on amphetamines. The individual and combined effects of rhynchophylline and ketamine on proliferation and GluN1 and GluA2/3 protein expression in PC12 cells were investigated. PC12 cells were differentiated into neuron-like cells by treatment with nerve growth factor (50 ng/mL). After treatment for 48 h, differentiated PC12 cell proliferation and GluN1 and GluA2/3 protein expression were analyzed. The viability of PC12 cells was reduced by ketamine at doses of 0.50, 1.00, 1.50, and 2.00 mmol/L, with the viability of cells treated with 1.50 and 2.00 mmol/L of ketamine significantly lower than that of the control cells. However, PC12 cells treated with rhynchophylline showed no toxicity at doses of 0.25, 0.50, 0.75, or 1.00 mmol/L. While GluA2/3 protein expression was upregulated by ketamine, it was not influenced by rhynchophylline. GluN1 protein expression was downregulated by rhynchophylline (1 mmol/L), while treatment with ketamine, either alone or with rhynchophylline, had no effect. These findings demonstrate that rhynchophylline suppresses GluA2/3 expression in ketamine-induced PC12 cells and downregulates GluN1 expression. Ketamine's lack of effect on GluN1 expression offers a partial explanation for ketamine addiction and the anti-addictive properties of rhynchophylline.
Base for Drug Clinical Trial, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, PR China.
Ji-Yin
JY
Zhou
Jin
J
Chen
Shi-Wen
SW
Zhou
Zhi-Xian
ZX
Mo
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D026121:Indole Alkaloids / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000078183:Oxindoles; D016716:PC12 Cells; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000209:etiology*
D002352:Carrier Proteins; D018691:Excitatory Amino Acid Antagonists; D026121:Indole Alkaloids; D007649:Ketamine; D009419:Nerve Tissue Proteins; D000078183:Oxindoles; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C121673:Gprin1 protein, mouse; C052714:rhyncophylline; C104722:glutamate receptor ionotropic, AMPA 2