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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.

We investigated which VIP receptors and coupled transduction pathways were involved in VIP enhancement of K⁺‐evoked [³H]‐GABA release from isolated nerve terminals of rat hippocampus.

VIP enhancement of [³H]‐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 …