title: Low concentrations of methamidophos do not alter AChE activity but modulate neurotransmitters uptake in hippocampus and striatum in vitro.
abstract: OBJECTIVE
  Methamidophos (Meth) is a toxic organophosphorus compound (OP) that inhibits acetylcholinesterase enzyme (AChE) and induces neurotoxicity. As the mechanism of its neurotoxic effects is not well understood, the aim of the present study was to evaluate the effects of Meth on glutamate and gamma aminobutyric acid (GABA) uptake and correlate with cell viability and AChE and Na(+)/K(+)-ATPase enzyme activities in striatum and hippocampus slices exposed to low concentrations (0.05 to 1.0 μM) of Meth.
  
  
  METHODS
  Hippocampal and striatal slices of rat brain were exposed to Meth for 5 min ([(3)H]Glutamate uptake) or 15 min ([(3)H]GABA uptake) for assays. The enzyme activities and cell viability were also accessed at both times in hippocampal and striatal slices and homogenates.
  
  
  RESULTS
  At concentrations that did not inhibit AChE, Meth caused changes in glutamate uptake in striatal (0.05 and 1.0 μM Meth) and hippocampal (1.0 μM Meth) slices. GABA uptake was increased by the pesticide in striatum at 0.5 and 1.0 μM and in hippocampus at 0.05 μM. After 3.5h of Meth exposure, striatal and hippocampal cells showed no changes in viability as well as no inhibition of Na(+)/K(+)-ATPase were observed after 5 or 15 min exposure to Meth in the same brain structures.
  
  
  CONCLUSIONS
  Results suggest that Meth, even without changing the AChE activity can modify somehow the neurotransmitters uptake. However, further studies are necessary to clarify if this modulation in glutamate or GABA uptake may be responsible to cause some disturbance in behavior or in other neurochemical parameters following low Meth exposure in vivo.
authors.affiliation: Departamento de Química, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, Campus UFSM, Santa Maria, RS, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: Gubert
authors.forename: Daiana Silva
authors.initials: DS
authors.lastname: Avila
authors.forename: Jessika Cristina
authors.initials: JC
authors.lastname: Bridi
authors.forename: Sara
authors.initials: S
authors.lastname: Saurin
authors.forename: Thiago Henrique
authors.initials: TH
authors.lastname: Lugokenski
authors.forename: Jardel Gomes
authors.initials: JG
authors.lastname: Villarinho
authors.forename: Roselei
authors.initials: R
authors.lastname: Fachinetto
authors.forename: Maria Ester
authors.initials: ME
authors.lastname: Pereira
authors.forename: Juliano
authors.initials: J
authors.lastname: Ferreira
authors.forename: João Batista Teixeira
authors.initials: JB
authors.lastname: da Rocha
authors.forename: Félix Alexandre Antunes
authors.initials: FA
authors.lastname: Soares
mesh_terms: D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009946:Organothiophosphorus Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D018377:Neurotransmitter Agents; D009946:Organothiophosphorus Compounds; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C014655:methamidophos; D000110:Acetylcholinesterase; D000254:Sodium-Potassium-Exchanging ATPase