Fernando K C, Barritt G J
Department of Medical Biochemistry, School of Medicine, Flinders University, Adelaide, Australia.
Biochim Biophys Acta. 1994 Jul 21;1222(3):383-9. doi: 10.1016/0167-4889(94)90044-2.
The inhibition of agonist-stimulated divalent cation inflow in hepatocytes by Gd3+ and compound SK&F 96365 (1-[beta-[3-(4-methoxyphenyl)propoxy]-4-methoxyphenethyl]-1H-imidazole hydrochloride) was investigated. Gd3+ and SK&F 96365 inhibited Ca2+ and Mn2+ inflow stimulated by vasopressin, angiotensin II or phenylephrine. The concentrations of Gd3+ and SK&F 96365 which gave half-maximal inhibition of vasopressin-stimulated Ca2+ inflow were 2 x 10(-7) M and 16 x 10(-6) M, respectively. The action of Gd3+ on vasopressin-stimulated Ca2+ inflow was rapid (less than 10 s in onset) and reversible. Gd3+ had no effect on Mn2+ inflow in the absence of an agonist and no effect on the ability of vasopressin to release Ca2+ from intracellular stores. SK&F 96365 inhibited Mn2+ inflow in the absence of agonists and vasopressin-induced release of Ca2+ from intracellular stores, but at approximately a 5-fold higher concentration than that which inhibited vasopressin-stimulated divalent cation inflow. It is concluded that Gd3+ and SK&F 96365 (at concentrations below 20 microM) inhibit, in a selective manner, divalent cation movement through the putative cation channel of the hepatocyte receptor-activated Ca2+ inflow system. Gd3+ appears to be the most potent inhibitor of this Ca2+ inflow system so far described.
研究了钆离子（Gd3+）和化合物SK&F 96365（1-[β-[3-(4-甲氧基苯基)丙氧基]-4-甲氧基苯乙]-1H-咪唑盐酸盐）对激动剂刺激的肝细胞二价阳离子内流的抑制作用。Gd3+和SK&F 96365抑制了由血管加压素、血管紧张素II或去氧肾上腺素刺激引起的Ca2+和Mn2+内流。对血管加压素刺激的Ca2+内流产生半数最大抑制作用时，Gd3+和SK&F 96365的浓度分别为2×10(-7)M和16×10(-6)M。Gd3+对血管加压素刺激的Ca2+内流的作用迅速（起效时间小于10秒）且可逆。在无激动剂时，Gd3+对Mn2+内流无影响，对血管加压素从细胞内储存库释放Ca2+的能力也无影响。SK&F 96365在无激动剂时抑制Mn2+内流，并抑制血管加压素诱导的Ca2+从细胞内储存库释放，但所需浓度比抑制血管加压素刺激的二价阳离子内流时高约5倍。结论是，Gd3+和SK&F 96365（浓度低于20 microM时）以选择性方式抑制二价阳离子通过肝细胞受体激活的Ca2+内流系统的假定阳离子通道移动。Gd3+似乎是迄今为止所描述的该Ca2+内流系统最有效的抑制剂。
