Parvez 2010 Biochim Biophys Acta

Parvez S, Winkler-Stuck K, Hertel S, Schoenfeld P, Siemen D (2010) The dopamine-D2-receptor agonist ropinirole dose-dependently blocks the Ca(2+)-triggered permeability transition of mitochondria. Biochim Biophys Acta 1797: 1245-1250.

» PMID: 20144882

Parvez S, Winkler-Stuck K, Hertel S, Schoenfeld P, Siemen D (2010) Biochim Biophys Acta

Abstract: Ropinirole, an agonist of the post-synaptic dopamine D2-receptor, exerts neuroprotective activity. The mechanism is still under discussion. Assuming that this neuroprotection might be associated with inhibition of the apoptotic cascade underlying cell death, we examined a possible effect of ropinirole on the permeability transition pore (mtPTP) in the mitochondrial inner membrane. Using isolated rat liver mitochondria, the effect of ropinirole was studied on Ca²⁺-triggered large amplitude swelling, membrane depolarization and cytochrome c release. In addition, the effect of ropinirole on oxidation of added, membrane-impermeable NADH was investigated. The results revealed doubtlessly, that ropinirole can inhibit permeability transition. In patch-clamp experiments on mitoplasts, we show directly that ropinirole interacts with the mtPTP. Thus, ropinirole reversibly inhibits the opening of mtPTP with an IC(50) of 3.4microM and a Hill coefficient of 1.3. In both systems (i.e. energized mitochondria and mitoplasts) the inhibitory effect on permeability transition was attenuated by increasing concentrations of inorganic phosphate. In addition, we showed with antimycin A-treated mitochondria that ropinirole failed to suppress respiratory chain-linked reactive oxygen species release. In conclusion, our data suggest that the neuroprotective activity of ropinirole is due to the blockade of the Ca²⁺-triggered permeability transition. • Keywords: Parkinson's disease, Permeability transition, Apoptosis, Mitochondria, Ropinirole, Neuroprotection

• O2k-Network Lab: DE Magdeburg Siemen D, DE Magdeburg Klinik Neurologie

Labels: Pathology: Parkinson's disease"Parkinson's disease" is not in the list (Aging;senescence, Alzheimer's, Autism, Cancer, Cardiovascular, COPD, Diabetes, Inherited, Infectious, Myopathy, ...) of allowed values for the "Diseases" property. 

Organism: Rat  Tissue;cell: Liver  Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property., Enzyme  Enzyme: Inner mtMembrane Transporter"Inner mtMembrane Transporter" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. 

Coupling state: OXPHOS 

HRR: Oxygraph-2k 

Abbreviations: CsA, cyclosporin A; Cyt c, cytochrome c; FCCP, carbonyl cyanide 4-(trifluoromethoxy)phenylhydrazone; IC50, inhibitor concentration causing 50% inhibition; mtPTP, mitochondrial permeability transition pore; PD, Parkinson's disease; RBM, rat brain mitochondria; RLM, rat liver mitochondria; ROS, reactive oxygen species; Pi, inorganic phosphate; Po, open probability; Δψm, mitochondrial membrane potential