Ely J A, Hunyady L, Baukal A J, Catt K J
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Biochem J. 1990 Jun 1;268(2):333-8. doi: 10.1042/bj2680333.
In bovine adrenal microsomes, Ins(1,4,5)P3 binds to a specific high-affinity receptor site (Kd = 11 nM) with low affinity for two other InsP3 isomers, Ins(1,3,4)P3 and Ins(2,4,5)P3. In the same subcellular fractions Ins(1,4,5)P3 was also the most potent stimulus of Ca2+ release of all the inositol phosphates tested. Of the many inositol phosphates recently identified in angiotensin-II-stimulated adrenal glomerulosa and other cells, Ins(1,3,4,5)P4 has been implicated as an additional second messenger that may act in conjunction with Ins(1,4,5)P3 to elicit Ca2+ mobilization. In the present study, an independent action of Ins(1,3,4,5)P4 was observed in bovine adrenal microsomes. Heparin, a sulphated polysaccharide which binds to Ins(1,4,5)P3 receptors in several tissues, inhibited both the binding of radiolabelled Ins(1,4,5)P3 and its Ca2(+)-releasing activity in adrenal microsomes. In contrast, heparin did not inhibit the mobilization of Ca2+ by Ins(1,3,4,5)P4, even at doses that abolished the Ins(1,4,5)P3 response. Such differential inhibition of the Ins(1,4,5)P3- and Ins(1,3,4,5)P4-induced Ca2+ responses by heparin indicates that Ins(1,3,4,5)P4 stimulates the release of Ca2+ from a discrete intracellular store, and exerts this action via a specific receptor site that is distinct from the Ins(1,4,5)P3 receptor.
在牛肾上腺微粒体中，肌醇-1,4,5-三磷酸（Ins(1,4,5)P3）与一个特定的高亲和力受体位点结合（解离常数Kd = 11 nM），而对其他两种肌醇三磷酸异构体，即肌醇-1,3,4-三磷酸（Ins(1,3,4)P3）和肌醇-2,4,5-三磷酸（Ins(2,4,5)P3）的亲和力较低。在相同的亚细胞组分中，Ins(1,4,5)P3也是所有测试的肌醇磷酸中对钙离子释放最有效的刺激物。在最近在血管紧张素II刺激的肾上腺球状带和其他细胞中鉴定出的众多肌醇磷酸中，肌醇-1,3,4,5-四磷酸（Ins(1,3,4,5)P4）被认为是一种额外的第二信使，可能与Ins(1,4,5)P3协同作用以引发钙离子动员。在本研究中，在牛肾上腺微粒体中观察到了Ins(1,3,4,5)P4的独立作用。肝素是一种硫酸化多糖，它在几种组织中与Ins(1,4,5)P3受体结合，抑制肾上腺微粒体中放射性标记的Ins(1,4,5)P3的结合及其钙离子释放活性。相反，即使在消除Ins(1,4,5)P3反应的剂量下，肝素也不抑制Ins(1,3,4,5)P4引起的钙离子动员。肝素对Ins(1,4,5)P3和Ins(1,3,4,5)P4诱导的钙离子反应的这种差异抑制表明，Ins(1,3,4,5)P4从一个离散的细胞内储存库刺激钙离子释放，并通过一个与Ins(1,4,5)P3受体不同的特定受体位点发挥这种作用。
