The Mitochondrial Targets of Neuroprotective Drug Vinpocetine on Primary Neuron Cultures, Brain Capillary Endothelial Cells, Synaptosomes, and Brain Mitochondria.

Abstract

Vinpocetine is considered as neuroprotectant drug and used for treatment of brain ischemia and cognitive deficiencies for decades. A number of enzymes, channels and receptors can bind vinpocetine, however the mechanisms of many effects' are still not clear. The present study investigated the effects of vinpocetine from the mitochondrial bioenergetic aspects. In primary brain capillary endothelial cells the purinergic receptor-stimulated mitochondrial Ca2+ uptake and efflux were studied. Vinpocetine exerted a partial inhibition on the mitochondrial calcium efflux. In rodent brain synaptosomes vinpocetine (30 μM) inhibited respiration in uncoupler stimulated synaptosomes and decreased H2O2 release from the nerve terminals in resting and in complex I inhibited conditions, respectively. In isolated rat brain mitochondria using either complex I or complex II substrates leak respiration was stimulated, but ADP-induced respiration was inhibited by vinpocetine. The stimulation of oxidation was associated with a small extent of membrane depolarization. Mitochondrial H2O2 production was inhibited by vinpocetine under all conditions investigated. The most pronounced effects were detected with the complex II substrate succinate. Vinpocetine also mitigated both Ca2+-induced mitochondrial Ca2+-release and Ca2+-induced mitochondrial swelling. It lowered the rate of mitochondrial ATP synthesis, while increasing ATPase activity. These results indicate more than a single mitochondrial target of this vinca alkaloid. The relevance of the affected mitochondrial mechanisms in the anti ischemic effect of vinpocetine is discussed.

• Authors: Gergely Svab, Judit Doczi, Akos A Gerencser, Attila Ambrus, Ferenc Gallyas, Balazs Sümegi, László Tretter
• Journal: Neurochemical research (Neurochem Res) Vol. 44 Issue 10 Pg. 2435-2447 (Oct 2019) ISSN: 1573-6903 [Electronic] United States
• PMID: 31535355 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Vinca Alkaloids
• vinpocetine
• Hydrogen Peroxide
• Calcium

Topics

• Animals
• Brain (drug effects, metabolism)
• Calcium (metabolism)
• Endothelial Cells (drug effects, metabolism)
• Hydrogen Peroxide (metabolism)
• Membrane Potential, Mitochondrial (drug effects)
• Mitochondria (drug effects, metabolism)
• Neurons (drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Rats, Wistar
• Synaptosomes (drug effects, metabolism)
• Vinca Alkaloids (pharmacology)