α_1肾上腺素受体激动剂的亚型选择性

采用放射配基竞争抑制实验和收缩功能实验相结合的方法，比较几种α１肾上腺素受体（α１－ＡＲ）激动剂对α１－ＡＲ两种亚型亲和性的异同，在放射配基竞争抑制实验中，以氯乙基可乐定预温育的海马粗制细胞膜标本中的α１－ＡＲ代表α１Ａ－ＡＲ亚型，以纯化的肝细胞膜标本中的α１－ＡＲ代表α１Ｂ－ＡＲ亚型，显示去甲肾上腺素，苯福林和Ａ５７２１９对两种α１－ＡＲ亚型的ｐＫｉ值无明显差异，而甲氧明和羟甲唑啉对α１Ａ－ＡＲ亚型的ｐＫｉ值显著大于α１Ｂ－ＡＲ亚型，离体血管收缩实验中，以氯乙基可乐定预温育的肾动脉和硝苯地平存在下的主动脉中，α１－ＡＲ介导的收缩分别代表α１Ａ－和α１Ｂ－ＡＲ亚型介导的生物效应，结果显示，苯福林在两种血管收缩实验中表现解离常数Ｋａｐｐ值无显著性差异，而甲氧明和羟甲唑啉的Ｋａｐｐ值则在肾动脉显著小于主动脉。上述结果提示去甲肾上腺素，苯福林和Ａ５７２１９对α１－ＡＲ的两种亚型没有选择性，而甲氧明与羟甲唑啉对α１Ａ－ＡＲ亚型的亲和性明显大于α１Ｂ－ＡＲ亚型。

Subtype selectivity of α1-adrenoceptor agonists

The differences of affinities of. fivealpha adrenoceptor ago nists for the two subtypes ofaloa1-adrenoceptor(α1-AR)were studied byradioligand bindi ng assavs in rat liver andhippocampus and the vasoconstriction experiments inrat aortae and renal arteries.In radioligand bindingassays,the α1-AR in crude hippocampus fraction in-cubated in 50 μmol·L-1 chlorethvlclonidine actedas α1A-AR subtype,the adrenoceptor in purified livermembrane acted as α1B-AR subtype. Fiveα1-adrenoceptor agonists were used to compete with[125I]BE2254 for binding in liver and hippocampus.The results showed that the pKi values ofnorepinephrine,phenylephrine or A 57219 for α1A-and α1B-AR were not different,while the pKi valuesof methoxamine and oxymetazoline for α1A-ARsubtype were significantly larger than those forα1B-AR subtype. In vasoconstriction experiments us-ing isolated blood vessels, ring preparation of aortaeand renal arteries were perfused in Krebs′solutioncontaiulng 1 μmol·L-1 propranolol and 0.1 μmol·L-1 yohimbine. The α1-AR in renal artery incubatedin 50 μmol·L-1 chlorethvlclonidine acted asα1A-AR. The α1-AR of aortae in presence of10 μmol·L-1 nifedipine acted as α1B-AR. The Kappvalues between α1A-and α1B-AR were not differentfor phenylephrine. The Kapp values of α1B-AR(225±43 and 7± μmol·L-1 for methoxamine andoxymetazoline)were larger than those of α1A-AR(37±9and 1.9±0.1 μmol·L-1 for methoxamine andoxymetazoline).These experiments suggested thatthere was no selectivity between α1A-and α1B-AR fornorepinephrine,phenylephrine,A57219 and that theaffinities of α1A-AR for methoxamine andoxymetazoline were obviously larger than those ofα1B-AR.