title: Intrastriatal neurotoxin injections reduce in vitro and in vivo binding of radiolabeled rotenoids to mitochondrial complex I.
abstract: The in vivo and in vitro bindings of radiolabeled rotenoids to mitochondrial complex I of rat striatum were examined after unilateral intrastriatal injections of quinolinic acid or 1-methyl-4-phenylpyridinium salt (MPP+). Quinolinic acid produced significant, similar losses of in vivo binding of [11C]dihydrorotenol ([11C]DHROL: 40%) and in vitro binding of [3H]dihydrorotenone ([3H]DHR: 53%) in the injected striatal at 13 days after the injection of neurotoxin. MPP+ reduced in vivo binding of [11C]DHROL up to-55%) as measured 1.5 to 6 h after its administration. Reductions of in vivo [11C]DHROL binding after either quinolinic acid or MPP+ injections did not correlate with changes in striatal blood flow as measured with [14C]iodoantipyrine. These results are consistent with losses of complex I binding sites for radiolabeled rotenoids, produced using cell death (quinolinic acid) or direct competition for the binding site (MPP+). Appropriately radiolabeled rotenoids may be useful for in vivo imaging studies of changes of complex I in neurodegenerative diseases.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0552, USA.
authors.forename: M R
authors.initials: MR
authors.lastname: Kilbourn
authors.forename: A
authors.initials: A
authors.lastname: Charalambous
authors.forename: K A
authors.initials: KA
authors.lastname: Frey
authors.forename: P
authors.initials: P
authors.lastname: Sherman
authors.forename: D S
authors.initials: DS
authors.lastname: Higgins
authors.forename: J T
authors.initials: JT
authors.lastname: Greenamyre
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D003342:Corpus Striatum / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D007267:Injections; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009498:Neurotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D017378:Quinolinic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D012402:Rotenone / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C095746:2-methoxy-6',7'-dihydrorotenol; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D012402:Rotenone; C044985:1',2'-dihydrorotenone; D016660:NAD(P)H Dehydrogenase (Quinone); D017378:Quinolinic Acid; D015655:1-Methyl-4-phenylpyridinium