科研之友
微信
新浪微博
Facebook
分享链接
摘要
Emerging evidence has suggested that inhibitory glycine receptors (GlyRs) are an important molecular target in the treatment of numerous neurological disorders. Rhizoma curcumae is a medicinal plant with positive neurological effects. In this study, we showed that curcumol, a major bioactive component of R. curcumae, reversibly and concentration-dependently inhibited the glycine-activated current (I-Gly) in cultured rat hippocampal neurons. The inhibitory effect was neither voltage-nor agonist concentration-dependent. Moreover, curcumol selectively inhibited homomeric alpha 2-containing, but not alpha 1- or alpha 3-containing, GlyRs. The addition of beta subunit conferred the curcumol sensitivity of alpha 3-containing, but not alpha 1-containing, GlyRs. Site-directed mutagenesis analysis revealed that a threonine at position 59 of the alpha 2 subunit is critical for the susceptibility of GlyRs to curcumol-mediated inhibition. Furthermore, paralleling a decline of alpha 2 subunit expression during spinal cord development, the degree of I-Gly inhibition by curcumol decreased with prolonged culture of rat spinal dorsal horn neurons. Taken together, our results suggest that the GlyRs are novel molecular targets of curcumol, which may underlie its pharmaceutical effects in the central nervous system.
