Energy-dependent accumulation of neuron blockers causes selective inhibition of neurotransmitter uptake by brain synaptic vesicles

Yoshinori Moriyama, Hui Lo Tsai, Masamitsu Futai

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The effects of neuron blockers on neurotransmitter accumulation in synaptic vesicles were investigated. Upon addition of ATP, brain synaptic vesicles accumulated chlorpromazine, haloperidol, and propranonol against concentration gradients of more than 100-fold. Bioenergetic analysis indicated that the transmembrane pH gradient (ΔpH) established by the vacuolar-type H+-ATPase is a direct driving force for these uptakes. Essentially the same results were obtained with vesicles from bovine adrenal chromaffin granules and proteoliposomes reconstituted with purified vacuolar H+-ATPase, indicating that the energy-dependent accumulation is due to diffusion and does not involve transport carriers specific for the blockers. Incubations of the two organelles with the blockers resulted in dissipation of ΔpH and slight increase of membrane potential (ΔΨ) without affecting ATPase activity. Under the same conditions, uptake of dopamine or γ-aminobutyrate (ΔpH-driven transport) was inhibited by neuron blockers, whereas uptake of glutamate (ΔΨ-driven transport) was slightly stimulated. Thus, neuron blockers inhibited ΔpH-driven uptake of neurotransmitter by dissipating the driving force. These results strongly suggest that synaptic vesicles are one of the target sites of neuron blockers.

Original languageEnglish
Pages (from-to)278-281
Number of pages4
JournalArchives of Biochemistry and Biophysics
Volume305
Issue number2
DOIs
Publication statusPublished - Jan 1 1993

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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