VIP enhances synaptic transmission to hippocampal CA1 pyramidal cells through activation of both VPAC1 and VPAC2 receptors.
We previously described that vasoactive intestinal peptide (VIP) increases synaptic transmission to hippocampal CA1 pyramidal cells at concentrations known to activate VIP-selective receptors (VPAC1 and VPAC2) but not the PACAP-selective PAC1 receptor. We now investigated the involvement of VPAC1 and VPAC2 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 VPAC1 or VPAC2 receptors with PG 97-269 (100 nM) or PG 99-465 (100 nM) inhibited VIP-induced enhancement of synaptic transmission. Selective activation of VPAC1 receptors with [K15, R16, L27] VIP(1-7)/GRF(8-27) (10 nM) or of VPAC2 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 microM) or PKC with GF109203X (1 microM) attenuated the effect of VIP (1 nM). GF109203X (1 microM) abolished the effect of the VPAC1 agonist [K15, R16, L27] VIP(1-7)/GRF(8-27) (10 nM) on hippocampal synaptic transmission but that effect was not changed by H-89 (1 microM). The effect of RO 25-1553 (100 nM) obtained in the presence of both the PAC1 and VPAC1 antagonists, M65 (30 nM) and PG 97-269 (100 nM), was strongly inhibited by H-89 (1 microM) but not GF109203X (1 microM). It is concluded that VIP enhances synaptic transmission to CA1 pyramidal cell dendrites through VPAC1 and VPAC2 receptor activation. VPAC1-mediated actions are dependent on PKC activity, and VPAC2-mediated actions are responsible for the PKA-dependent actions of VIP on CA1 hippocampal transmission.
Cunha-Reis
Diana
D
Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal. diana-reis@fm.ul.pt
Ribeiro
Joaquim Alexandre
JA
Sebastião
Ana M
AM
D000818:Animals; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D018005:Receptors, Vasoactive Intestinal Peptide / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D054746:Cyclic AMP-Dependent Protein Kinase Type II; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C