VPAC1 and VPAC2 receptor activation on GABA release from hippocampal nerve terminals involve several different signalling pathways.
Br J Pharmacol
; 174(24): 4725-4737, 2017 Dec.
Article
em En
| MEDLINE
| ID: mdl-28945273
ABSTRACT
BACKGROUND AND PURPOSE:
Vasoactive intestinal peptide (VIP) is an important modulator of hippocampal synaptic transmission that influences both GABAergic synaptic transmission and glutamatergic cell excitability through activation of VPAC1 and VPAC2 receptors. Presynaptic enhancement of GABA release contributes to VIP modulation of hippocampal synaptic transmission. EXPERIMENTALAPPROACH:
We investigated which VIP receptors and coupled transduction pathways were involved in VIP enhancement of K+ -evoked [3 H]-GABA release from isolated nerve terminals of rat hippocampus. KEYRESULTS:
VIP enhancement of [3 H]-GABA release was potentiated in the presence of the VPAC1 receptor antagonist PG 97-269 but converted into an inhibition in the presence of the VPAC2 receptor antagonist PG 99-465, suggesting that activation of VPAC1 receptors inhibits and activation of VPAC2 receptors enhances, GABA release. A VPAC1 receptor agonist inhibited exocytotic voltage-gated calcium channel (VGCC)-dependent [3 H]-GABA release through activation of protein Gi/o , an effect also dependent on PKC activity. A VPAC2 receptor agonist enhanced both exocytotic VGCC-dependent release through protein Gs -dependent, PKA-dependent and PKC-dependent mechanisms and GABA transporter 1-mediated [3 H]-GABA release through a Gs protein-dependent and PKC-dependent mechanism. CONCLUSIONS AND IMPLICATIONS Our results show that VPAC1 and VPAC2 VIP receptors have opposing actions on GABA release from hippocampal nerve terminals through activation of different transduction pathways. As VPAC1 and VPAC2 receptors are located in different layers of Ammon's horn, our results suggest that these VIP receptors underlie different modulation of synaptic transmission to pyramidal cell dendrites and cell bodies, with important consequences for their possible therapeutic application in the treatment of epilepsy.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Receptores Tipo II de Peptídeo Intestinal Vasoativo
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Receptores Tipo I de Polipeptídeo Intestinal Vasoativo
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Ácido gama-Aminobutírico
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Hipocampo
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article