Worley P F, Baraban J M, Supattapone S, Wilson V S, Snyder S H
J Biol Chem. 1987 Sep 5;262(25):12132-6.
Inositol 1,4,5-trisphosphate is an intracellular second messenger, produced upon stimulation of the phosphoinositide system, capable of mobilizing calcium from intracellular stores. We have recently identified high levels of specific binding sites for inositol 1,4,5-trisphosphate in brain membranes (Worley, P. F., Baraban, J. M., Colvin, J. S., and Snyder, S. H. (1987) Nature 325, 159-161) and have now further characterized these sites. In cerebellar membranes, inositol 1,4,5-trisphosphate binding sites are abundant (20 pmol/mg protein) and display high affinity and selectivity for inositol 1,4,5-trisphosphate (KD approximately equal to 40 nM), whereas other inositol phosphates such as inositol 1,3,4,5-tetrakisphosphate (Ki approximately equal to 10 microM) and inositol 1,4-bisphosphate (Ki approximately equal to 10 microM) exhibit much lower affinity for this site. Submicromolar concentrations of calcium strongly inhibit inositol 1,4,5-trisphosphate binding (IC50 approximately equal to 300 nM). A sharp increase in binding occurs at slightly alkaline pH. These results suggest that actions of inositol 1,4,5-trisphosphate are regulated by physiological alterations in intracellular pH and calcium concentrations.
肌醇1,4,5-三磷酸是一种细胞内第二信使，在磷酸肌醇系统受到刺激时产生，能够从细胞内储存库中动员钙。我们最近在脑膜中发现了高水平的肌醇1,4,5-三磷酸特异性结合位点（沃利，P.F.，巴拉班，J.M.，科尔文，J.S.，和斯奈德，S.H.（1987年）《自然》325，159 - 161），现在对这些位点进行了进一步的表征。在小脑膜中，肌醇1,4,5-三磷酸结合位点丰富（20 pmol/mg蛋白质），对肌醇1,4,5-三磷酸表现出高亲和力和选择性（KD约等于40 nM），而其他肌醇磷酸，如肌醇1,3,4,5-四磷酸（Ki约等于10 microM）和肌醇1,4-二磷酸（Ki约等于10 microM）对该位点的亲和力要低得多。亚微摩尔浓度的钙强烈抑制肌醇1,4,5-三磷酸的结合（IC50约等于300 nM）。在略碱性pH值下结合会急剧增加。这些结果表明，肌醇1,4,5-三磷酸的作用受细胞内pH值和钙浓度的生理变化调节。
