[3H]-DA release evoked by low pH medium and internal H+ accumulation in rat hypothalamic synaptosomes: involvement of calcium ions

Roberto Monastero, Carla Cannizzaro, Maria Martire, Michele Vacca

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30 Citations (Scopus)


The pH fluctuations have been often interpreted as an insufficient regulation or as a consequence of the onset of pathological events, such asischemia, in which a significant decrease in pH levels occurs. Neurotransmitter release appears to be affected by pH drop significantly. In thisstudy, we investigated the effect of an extracellular and an intracellular acidification on tritiated dopamine release ([3H]-DA release), fromsuperfused rat hypothalamic synaptosomes. When compared to basal release, extracellular acidification, due to a reduction in the externalpH of the nominally carbonic-free superfusion media, provoked a significant increase in [3H]-DA release that showed a sensitiveness tocalcium omission. Intraterminal acidification, obtained blocking the Na+/H+ exchanger by 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) and5-(N,N-dimethyl)-amiloride (DMA), induced a significant increase in [3H]-DA outflow which occurred in a calcium-dependent manner(80% inhibition in absence of calcium from superfusion media). To further promote an intraterminal acidification through a H+ inneraccumulation, the proton ionophore nigericin was used. At every dose employed (10 M), this compound induced a significant increasein [3H]-DA outflow, compared to basal release. Nigericin-evoked [3H]-DA release showed a 50% decrease when calcium was omittedfrom superfusion media. When BAPTA-AM, a chelator of intracellular calcium, was added, nigericin-evoked [3H]-DA was completelyabolished. These data indicate that [3H]-DA release can be induced by extracellular acidification due to a lowering of external pH and byan intraterminal acidification due to an internal proton accumulation. The mechanism that can trigger this exocytotic process appears todepend on calcium presence, and in particular, on an increased intraterminal calcium availability.
Original languageEnglish
Pages (from-to)9-17
Number of pages8
JournalNeurochemistry International
Publication statusPublished - 2003

All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

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