title: Sertraline inhibits pre-synaptic Na⁺ channel-mediated responses in hippocampus-isolated nerve endings.
abstract: In the present study, a possible sertraline action on cerebral pre-synaptic Na(+) channels was investigated. For this purpose, the effect of sertraline on responses induced by the Na(+) channel opener, veratridine, namely the increase in Na(+) and in neurotransmitter release in hippocampus-isolated nerve endings was investigated. Results show that sertraline in the low μM range (1.5-25 μM) progressively inhibits the rise in Na(+) and the release of pre-loaded [(3) H]Glu as well as the release of endogenous 5-HT, Glu and GABA (detected by HPLC) induced by veratridine depolarization either under external Ca(2+) -free conditions or in the presence of external Ca(2+) . In addition, under non-depolarized conditions, sertraline (25 μM) increased the external concentration of 5-HT at expense of its internal concentration, and unchanged the external and internal concentrations of the amino acid neurotransmitters and of the 5-HT main metabolite, 5-HIAA. This result is consistent with the sertraline inhibitory action of the serotonin transporter. However, sertraline is unlikely to inhibit pre-synaptic Na(+) channels permeability by increasing external 5-HT. Because 5-HT in a wide concentration range (1-1000 μM) did not change the veratridine-induced increase in Na(+) . In summary, present findings demonstrate that besides the inhibition of 5-HT reuptake, sertraline is an effective inhibitor of pre-synaptic Na(+) channels controlling neurotransmitter release.
authors.affiliation: Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad Universitaria, México D.F., México.
authors.forename: Blanca I
authors.initials: BI
authors.lastname: Aldana
authors.forename: María
authors.initials: M
authors.lastname: Sitges
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D020280:Sertraline / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018377:Neurotransmitter Agents; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012701:Serotonin; D018698:Glutamic Acid; D013779:Tetrodotoxin; D006897:Hydroxyindoleacetic Acid; D005680:gamma-Aminobutyric Acid; D014701:Veratridine; D012964:Sodium; D020280:Sertraline; D002118:Calcium