| pubmed-article:21139245 | pubmed:abstractText | The 5-HT? receptor (5-HT?R) is a member of the class of recently discovered 5-hydroxytryptamine (5-HT) receptors. Due to the lack of selective 5-HT?R ligands, the cellular signaling mechanisms of the 5-HT?R are poorly understood. We previously developed a cell-based high-throughput screening (HTS) method for the 5-HT?R and screened synthetic chemical compounds. In the present study, we expanded our screening into natural products to find novel 5-HT?R ligands. We found that the ethyl acetate fraction from the root of Caragana sinica (537-18BE) produced the most potent antagonistic activity. After further isolation of 537-18BE, we found that three stilbene derivatives, (+)-?-viniferin, miyabenol C and pallidol, are active constituents of 537-18BE inhibiting the 5-HT?R. Among them, (+)-?-viniferin showed the most potent inhibition, and miyabenol C also produced a considerable inhibition. When examined effects on other neurotransmitters for selectivity, 537-18BE and three stilbene derivatives did not produce any notable effects on 5-HT?, 5-HT?, or muscarinic acetylcholine M1 (M(1)) receptors. Furthermore, 5-HT?R antagonistic effects of (+)-?-viniferin, miyabenol C and pallidol were confirmed on extracellular signal-regulated kinase 1 and 2 (ERK1/2) which exerts effects in downstream pathways of 5-HT?R activation. | lld:pubmed |
