四氢原小檗碱同类物对α1肾上腺素受体的拮抗作用

用放射配体结合实验与离体血管收缩功能实验相结合的方法,研究了4种四氢原小檗碱(tetrahydroproberberine,THPB)同类物对α₁-肾上腺素受体(α₁-AR)的作用。结果显示左旋四氢巴马汀(l-THP),左旋千金藤立陡碱(l-SPD),四氢原小檗碱-18(THPB-18)和四氢小檗碱(THB)¹²⁵IBE2254¹²⁵I-2-β(4-hydroxyphenyl)-ethyaminomethyl-tetralone,¹²⁵IBE)与大鼠脑皮质α₁-AR的结合呈竞争性拮抗作用,pK_I值分别为5.54±0.36,5.56±0.47,5.75±0.56和6.01±0.60,Hill系数接近于1.0。并拮抗苯肾上腺素(phenylephrine,PE)介导大鼠主动脉的收缩,pA₂值分别为5.48±0.58,5.66±0.54,5.64±0.34和5.45±0.76,斜率与1.0无显著性差别。结果提示,4种四氢原小檗碱同类物对α₁-AR均有非亚型选择性拮抗效应,且亲和性相同。

ANTAGONISTIC EFFECT OF TETKAHYDKOPROBERBEKINE HOMOLOGUES ON α1-ADRENOCEPTOR

The antagonistic effect of tetrahydroproberberine(THP)homologues on α₁-adrenoceptor was studied by combination of radioligand binding assays and measurements ofvasoconstriction responses.The results showed that l-tetrahydropalmatine(l-THP),l- stepholidine(l-SPD),THPB-18 and tetrahydroberberine(THB)competitively inhibited the 125 I-BE2254 specificbinding in rat cerebral cortex with pK_I values of 5.54±0.36,5.56±0.47,5.75±0.56 and 6.01 ±0.60,respectively,and the Hill efficiency was not significantly different from unity.They inhibitedphenylephrine-induced constrictions with pA₂ values of 5.48 ± 0.58,5.66 ± 0.54,5.64 ± 0.34 and5.45 ± 0.76,respectively,and the slopes of Schild plot were not significantly different from unity。The results indicate that the 4 THP homologues are nonsubtype selective competitive antagonists forα₁