VIP enhances synaptic transmission to hippocampal CA1 pyramidal cells through activation of both VPAC 1 and VPAC 2 receptors

Abstract

We previously described that vasoactive intestinal peptide (VIP) increases synaptic transmission to hippocampal CA1 pyramidal cells at concentrations known to activate VIP-selective receptors (VPAC 1 and VPAC 2) but not the PACAP-selective PAC 1 receptor. We now investigated the involvement of VPAC 1 and VPAC 2 receptors in the effects elicited by VIP as well as the transduction pathways activated by VIP to cause enhancement of synaptic transmission. Blockade of either VPAC 1 or VPAC 2 receptors with PG 97–269 (100 nM) or PG 99–465 (100 nM) inhibited VIP-induced enhancement of synaptic transmission. Selective activation of VPAC 1 receptors with [K 15, R 16, L 27] VIP(1–7)/GRF(8–27) (10 nM) or of VPAC 2 receptors with RO 25–1553 (10 nM) increased synaptic transmission to CA1 pyramidal cells, and this increase was larger when both agonists were applied together. Inhibition of either PKA with H-89 (1 μM) or PKC with GF109203X (1 μM) attenuated the effect of VIP (1 nM). GF109203X (1 μM) abolished the effect of the VPAC 1 agonist [K 15, R 16, L 27] VIP(1–7)/GRF(8–27) (10 nM) on hippocampal synaptic transmission but that effect was not changed by H-89 (1 μM). The effect of RO 25–1553 (100 nM) obtained in the presence of both the PAC 1 and VPAC 1 antagonists, M65 (30 nM) and PG 97–269 (100 nM), was strongly inhibited by H-89 (1 μM) but not GF109203X (1 μM). It is concluded that VIP enhances synaptic transmission to CA1 pyramidal cell dendrites through VPAC 1 and VPAC 2 receptor activation. VPAC 1-mediated actions are dependent on PKC activity, and VPAC 2-mediated actions are responsible for the PKA-dependent actions of VIP on CA1 hippocampal transmission.