期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1993
卷号：90
期号：20
页码：9523-9527
DOI：10.1073/pnas.90.20.9523
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：A pharmacologically active agent was easily extracted by aqueous or organic solvents from laboratory plastic tubes (Falcon Blue Max) and has been chemically identified as bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate. This compound (approximately 12 micrograms per tube approximately 25 nmol) blocked 1,4-dihydropyridine-sensitive 45Ca2+ uptake into GH3 cells with an IC50 value of 3.6 microM, inhibited Sr2+ currents through L-type Ca2+ channels in A7r5 smooth-muscle cells in whole-cell patch-clamp experiments after extracellular application, and affected the high-affinity binding of Ca2+ entry-blocker ligands to a variety of preparations. Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is a highly potent (IC50 values < 10 nM) inhibitor at the phenylalkylamine- and benzothiazepine-selective drug-binding domains of the alpha 1 subunit of L-type Ca2+ channels. This compound behaves as a heterotropic allosteric regulator for the 1,4-dihydropyridine-selective domain in purified Ca(2+)-channel preparations from rabbit skeletal muscle. (+)-Tetrandrine stimulation of 1,4-dihydropyridine binding to the membrane-bound L-type Ca2+ channel is inhibited by the compound in a competitive manner (Ki value = 6.8 nM). Bis(2,2,6,6-tetramethyl-4-piperidyl) sebacate is therefore classified as the prototype of another class of L-type Ca(2+)-channel blockers that binds to the alpha 1 subunit at the drug-binding domains selective for (+)-tetrandrine or (+)-cis-diltiazem. This compound is identical to Tinuvin 770, which is used worldwide as a light stabilizer for polyolefins.
