论文部分内容阅读
Aim:To find human dopamine receptors,especially Dl-like receptor specific ago-nists from Chinese herbs as potential antihypertension drug leads.Methods:TwoD l-like receptor cell lines carrying a μ-lactamase reporter gene,and a D2 receptorcell line coexpressing a promiscuous G protein G15 were constructed using HEK293cells.A natural compound library made from fractionated samples of herbal ex-tracts was used for high-throughput screening(HTS)against one of the cell lines,HEK/D5R/CRE-blax.The interested hits were evaluated for their activities againstvarious dopamine receptors.Results:Fourteen hits were identified from primaryscreening,of which 2 of the better hit samples,HD0522 and HD0059,were selectedfor further material and activity analysis,and to obtain 2 compounds that ap-peared as 2 single peaks in HPLC,HD0522H01 and HD0059H01.HD0059H01could activate D 1,D2,and D5 receptors,with EC_(50)values of 2.28 μg/mL,0.85 μg/mL,and 1.41 μg/mL,respectively.HD0522H01 could only activate DlR and D5Rwith EC_(50)values of 2.95 μg/mL and 8.38 μg/mL.Conclusion:We established cell-based assays for 3 different human dopamine receptors and identified specificagonists HD0522H01 and HD0059H01 through HTS.The specific agonist to D1-like receptors,HD0522H01,may become a new natural product-based drug leadfor antihypertension treatment.
Aim:To find human dopamine receptors,especially Dl-like receptor specific ago-nists from Chinese herbs as potential antihypertension drug leads.Methods:Two D l-like receptor cell lines carrying a μ-lactamase reporter gene,and a D2 receptorcell line coexpressing a Promiscuous G protein G15 were constructed using HEK293cells.A natural compound library made from fractionated samples of herbal ex-tracts was used for high-throughput screening(HTS)against one of the cell lines,HEK/D5R/CRE-blax.The estimated hits We evaluated for their activity againstvarious dopamine receptors.Results:Fourteen hits were identified from primaryscreening,of which 2 of the better hit samples,HD0522 and HD0059, were selectedfor further material and activity analysis,and to obtain 2 compounds that ap-peared as 2 Single peaks in HPLC, HD0522H01 and HD0059H01.HD0059H01could activate D 1,D2,and D5 receptors,with EC_(50)values of 2.28 μg/mL,0.85 μg/mL,and 1.41 μg/mL,respectively.HD0522H01 may only activate Dl R and D5Rwith EC_(50)values of 2.95 μg/mL and 8.38 μg/mL.Conclusion:We established cell-based assays for 3 different human dopamine receptors and identified specificagonists HD0522H01 and HD0059H01 through HTS.The specific agonist to D1-like receptors ,HD0522H01,may become a new natural product-based drug leadfor antihypertension treatment.