PMID- 1900156 OWN - NLM STAT- MEDLINE DCOM- 19910403 LR - 20190623 IS - 0006-2952 (Print) IS - 0006-2952 (Linking) VI - 41 IP - 5 DP - 1991 Mar 1 TI - Inhibitory effects of two structurally related carbocyanine laser dyes on the activity of bovine heart mitochondrial and Paracoccus denitrificans NADH-ubiquinone reductase. Evidence for a rotenone-type mechanism. PG - 677-84 AB - Two cationic, lipophilic laser dyes, 1,1',3,3,3',3'-hexamethylindodicarbocyanine iodide (HIDC) and 1,1',3,3,3',3'-hexamethylindotricarbocyanine iodide (HITC), inhibit bovine heart mitochondrial and Paracoccus denitrificans NADH oxidase activities. The mitochondrial I50 values were 0.5 microM (HIDC) and 1.2 microM (HITC), and the P. denitrificans I50 values 1.2 microM (HIDC) and 1.5 microM (HITC). Neither succinate nor cytochrome oxidase (EC 1.9.3.1) activities were inhibited significantly by either compound, localizing the site of inhibition to the segment of each electron transport chain between NADH and ubiquinone. With submitochrondrial particles (SMP), NADH-dependent reduction of menadione, duroquinone and coenzyme Q1 was inhibited markedly (HIDC was the more potent inhibitor). Using purified complex I, only NADH-dependent reduction of duroquinone and coenzyme Q1 was inhibited markedly (HIDC was the more potent inhibitor) and reduction of menadione was inhibited slightly. With P. denitrificans membrane vesicles, NADH-dependent reduction of menadione, juglone, and coenzyme Q1 was inhibited slightly and duroquinone reduction was inhibited markedly. Membrane-dependent interactions appear to be involved, since the compounds were more inhibitory with membrane preparations than with complex I. The mechanism of inhibition (except for the HIDC effect on coenzyme Q1 reduction with P. denitrificans) appeared to be through the interaction of dye with the rotenone site on NADH-ubiquinone reductase (EC 1.6.99.3), since rotenone-insensitive preparations of complex I and P. denitrificans membrane vesicles were also insensitive to HIDC and HITC inhibition. FAU - Anderson, W M AU - Anderson WM AD - Indiana University School of Medicine, Northwest Center for Medical Education, Gary 46408. FAU - Chambers, B B AU - Chambers BB FAU - Wood, J M AU - Wood JM FAU - Benninger, L AU - Benninger L LA - eng GR - HL 32829/HL/NHLBI NIH HHS/United States PT - Comparative Study PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (Carbocyanines) RN - 0 (Fluorescent Dyes) RN - 03L9OT429T (Rotenone) RN - 16595-48-5 (1,1',3,3,3',3'-hexamethylindotricarbocyanine) RN - 48221-03-0 (1,1',3,3,3',3'-hexamethylindodicarbocyanine) RN - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone)) RN - EC 1.6.99.- (Quinone Reductases) SB - IM MH - Animals MH - Carbocyanines/*pharmacology MH - Cattle MH - Dose-Response Relationship, Drug MH - Electron Transport/drug effects MH - Fluorescent Dyes/*pharmacology MH - Mitochondria, Heart/*drug effects/enzymology MH - NAD(P)H Dehydrogenase (Quinone) MH - Paracoccus denitrificans/*drug effects/enzymology MH - Quinone Reductases/*metabolism MH - Rotenone/*pharmacology EDAT- 1991/03/01 00:00 MHDA- 1991/03/01 00:01 CRDT- 1991/03/01 00:00 PHST- 1991/03/01 00:00 [pubmed] PHST- 1991/03/01 00:01 [medline] PHST- 1991/03/01 00:00 [entrez] AID - 0006-2952(91)90066-E [pii] AID - 10.1016/0006-2952(91)90066-e [doi] PST - ppublish SO - Biochem Pharmacol. 1991 Mar 1;41(5):677-84. doi: 10.1016/0006-2952(91)90066-e.