PMID- 15843048
OWN - NLM
STAT- MEDLINE
DCOM- 20050630
LR  - 20181201
IS  - 0197-0186 (Print)
IS  - 0197-0186 (Linking)
VI  - 46
IP  - 7
DP  - 2005 Jun
TI  - Phenylarsine oxide is able to dissipate synaptic vesicle acidic pool.
PG  - 541-50
AB  - Phenylarsine oxide (PAO) has a number of targets in the neurons, one of them is 
      exocytotic process. In this study, we have focused on the mechanisms of 
      phenylarsine oxide action on Ca(2+)-dependent and Ca(2+)-independent 
      neurotransmitter release from rat brain synaptosomes. We investigated the 
      influence of phenylarsine oxide on: (i) l-[(14)C]glutamate and [(3)H]GABA release 
      and uptake; (ii) plasma membrane potential using a potential-sensitive 
      fluorescent probe rhodamine 6G; (iii) exo/endocytotic process using a 
      pH-sensitive fluorescent probe acridine orange (AO). It has been found that 
      phenylarsine oxide induced deacidification of synaptic vesicles. This effect was 
      completely abolished by preliminary treatment of synaptosomes with a protonophore 
      FCCP indicating that both reagents injured a proton electrochemical gradient. 
      Dissipation of the proton gradient by low concentrations of phenylarsine oxide 
      (not exceed 1 microM) did not prevent KCl-triggered exocytotic response, but 
      essentially modified endocytotic one. At higher concentrations of phenylarsine 
      oxide (up to 10 microM), the proton gradient dissipation was intensified and the 
      exocytotic response was fully abolished. The reagent did not change plasma 
      membrane potential, but depolarized mitochondria. It also caused potent 
      inhibition of the Ca(2+)-stimulated l-[(14)C]glutamate and [(3)H]GABA release and 
      increase the Ca(2+)-independent release of l-[(14)C]glutamate, but not of 
      [(3)H]GABA. Disulfide-reducing reagents (dithiothreitol and beta-mercaptoethanol) 
      completely prevented phenylarsine oxide-evoked injuries. They could also restore 
      the initial levels of the mitochondrial potential, the exocytotic response to KCl 
      and the release and uptake of neurotransmitters. Our data provide the evidence 
      that phenylarsine oxide causes dissipation of synaptic vesicle acidic pool 
      resulting in the reduction of vesicle filling and as consequence in attenuation 
      of Ca(2+)-stimulated neurotransmitter release.
FAU - Tarasenko, A S
AU  - Tarasenko AS
AD  - Department of Neurochemistry, Palladin Institute of Biochemistry, National 
      Academy of Sciences of Ukraine, Leontovich Str. 9, Kiev 01601, Ukraine.
FAU - Kostrzhevska, O G
AU  - Kostrzhevska OG
FAU - Storchak, L G
AU  - Storchak LG
FAU - Linetska, M V
AU  - Linetska MV
FAU - Borisova, T A
AU  - Borisova TA
FAU - Himmelreich, N H
AU  - Himmelreich NH
LA  - eng
PT  - Journal Article
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Arsenicals)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ionophores)
RN  - 0 (Neurotransmitter Agents)
RN  - 0HUR2WY345 (oxophenylarsine)
RN  - 370-86-5 (Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 660YQ98I10 (Potassium Chloride)
RN  - T8ID5YZU6Y (Dithiothreitol)
SB  - IM
MH  - Animals
MH  - Arsenicals/*pharmacology
MH  - Brain/*metabolism
MH  - Calcium Signaling/drug effects/physiology
MH  - Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology
MH  - Dithiothreitol/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Exocytosis/*drug effects/physiology
MH  - Glutamic Acid/metabolism
MH  - Hydrogen-Ion Concentration
MH  - Ionophores/pharmacology
MH  - Male
MH  - Membrane Potentials/drug effects/physiology
MH  - Mitochondria/drug effects/metabolism
MH  - Neurotransmitter Agents/*metabolism
MH  - Potassium Chloride/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Synaptic Transmission/drug effects/physiology
MH  - Synaptic Vesicles/*drug effects/*metabolism
MH  - Synaptosomes/chemistry/*drug effects/metabolism
MH  - gamma-Aminobutyric Acid/metabolism
EDAT- 2005/04/22 09:00
MHDA- 2005/07/01 09:00
CRDT- 2005/04/22 09:00
PHST- 2004/11/10 00:00 [received]
PHST- 2005/02/03 00:00 [revised]
PHST- 2005/02/03 00:00 [accepted]
PHST- 2005/04/22 09:00 [pubmed]
PHST- 2005/07/01 09:00 [medline]
PHST- 2005/04/22 09:00 [entrez]
AID - S0197-0186(05)00047-1 [pii]
AID - 10.1016/j.neuint.2005.02.004 [doi]
PST - ppublish
SO  - Neurochem Int. 2005 Jun;46(7):541-50. doi: 10.1016/j.neuint.2005.02.004.