title: A light stabilizer (Tinuvin 770) that elutes from polypropylene plastic tubes is a potent L-type Ca(2+)-channel blocker.
abstract: 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.
authors.affiliation: Institute für Biochemische Pharmakologie, Innsbruck, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Glossmann
authors.forename: S
authors.initials: S
authors.lastname: Hering
authors.forename: A
authors.initials: A
authors.lastname: Savchenko
authors.forename: W
authors.initials: W
authors.lastname: Berger
authors.forename: K
authors.initials: K
authors.lastname: Friedrich
authors.forename: M L
authors.initials: ML
authors.lastname: Garcia
authors.forename: M A
authors.initials: MA
authors.lastname: Goetz
authors.forename: J M
authors.initials: JM
authors.lastname: Liesch
authors.forename: D L
authors.initials: DL
authors.lastname: Zink
authors.forename: G J
authors.initials: GJ
authors.lastname: Kaczorowski
mesh_terms: D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D044182:Benzylisoquinolines; D001667:Binding, Competitive; D002121:Calcium Channel Blockers; D002460:Cell Line; D003652:Decanoic Acids / Q000494:pharmacology*; D004095:Dihydropyridines / Q000378:metabolism; D004110:Diltiazem / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D010880:Piperidines / Q000494:pharmacology*; D011126:Polypropylenes / Q000737:chemistry*; D011817:Rabbits; D013552:Swine; D014700:Verapamil / Q000378:metabolism
chemical_list: D000470:Alkaloids; D044182:Benzylisoquinolines; D002121:Calcium Channel Blockers; D003652:Decanoic Acids; D004095:Dihydropyridines; D010880:Piperidines; D011126:Polypropylenes; C009438:tetrandrine; C083752:Tinuvin 770; D014700:Verapamil; D004110:Diltiazem