Characterization of subtype of α_1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed

Characterization of subtype of α 1 adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed 1

目的：研究去甲肾上腺素（ＮＥ）介导大鼠肠系膜血管床（ＭＶＢ）收缩的α１肾上腺素受体（α１ＡＲ）亚型．方法：用灌流大鼠ＭＶＢ标本收缩功能实验和克隆细胞放射配体结合实验测定α１ＡＲ亚型选择性拮抗剂ｐＡ２和ｐＫｉ，并作相关分析．结果：α１ＡＡＲ选择性拮抗剂ＲＳ１７０５３、ＷＢ４１０１、５ＭＵ及α１ＤＡＲ选择性拮抗剂ＢＭＹ７３７８的ｐＡ２分别为８９８±０２８，９１６±０２０，８．６９±００２和６０３±０２６，Ｓｃｈｉｌｄ作图斜率值与１０差别无显著性．其ｐＡ２值与α１ＡＡＲ的ｐＫｉ相关系数为０９７，与α１Ｂ和α１ＤＡＲ的相关系数分别为０５２和００４．

AIM: To characterize the subtype of α 1 adrenoceptor mediating vasoconstriction in perfus￣ed rat mesenteric vascular bed. METHODS: The potencies (p A 2 values determined by Schild plot) of α 1 adrenoceptor selective antagonists were determined by isolated vaso￣constrictive experiment. The p K i values were determined by 125 I BE 2254 binding from the cloned α 1A , α 1B , and α 1D adrenoceptor, stably expressed in human embryonic kidney (HEK) 293 cells. RE￣SULTS: The p A 2 values for α 1A adrenoceptor selective antagonists, RS 17053, WB 4101, 5 methyl urapidil, and the α 1D adrenoceptor selective antagonist, BMY 7378, were 8 98±0 28, 9 16±0 20, 8 69±0 02, and 6 03±0 26, respectively, with the slope not different from unity. The p A 2 values of the above antagonists correlated well with the binding p K i values only for α 1A adrenoceptors ( r =0 97), but not for α 1B adrenoceptors ( r =0 52) and α 1D adrenoceptors ( r =0 04). The con￣cen￣tra￣tion vasopressor response curve for nor￣epine￣phrine was not affected by pretreatment with chloroethylclonidine (Chl) 50 μmol·L -1 for 30 min. CONCLUSION: Only α 1A adreno￣ce￣ptors mediate the norepinephrine induced vaso￣pres￣sor response in perfused rat mesenteric vascular bed.