血管活性肠肽通过激活VPAC1和VPAC2受体增强对海马CA1锥体细胞的突触传递。

VIP enhances synaptic transmission to hippocampal CA1 pyramidal cells through activation of both VPAC1 and VPAC2 receptors.

作者信息

Cunha-Reis Diana, Ribeiro Joaquim Alexandre, Sebastião Ana M

机构信息

Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Av. Prof. Egas Moniz, 1649-028 Lisbon, Portugal.

出版信息

Brain Res. 2005 Jul 5;1049(1):52-60. doi: 10.1016/j.brainres.2005.04.077.

DOI:10.1016/j.brainres.2005.04.077

PMID:15935995

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 (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.

摘要

我们之前曾描述过，血管活性肠肽（VIP）在已知能激活VIP选择性受体（VPAC1和VPAC2）但不能激活PACAP选择性PAC1受体的浓度下，可增强对海马CA1锥体神经元的突触传递。我们现在研究了VPAC1和VPAC2受体在VIP所引发效应中的作用，以及VIP激活以导致突触传递增强的转导途径。用PG 97 - 269（100 nM）或PG 99 - 465（100 nM）阻断VPAC1或VPAC2受体，可抑制VIP诱导的突触传递增强。用[K15, R16, L27] VIP(1 - 7)/GRF(8 - 27)（10 nM）选择性激活VPAC1受体或用RO 25 - 1553（10 nM）激活VPAC2受体，均可增强对CA1锥体神经元的突触传递，且当两种激动剂同时应用时，这种增强作用更大。用H - 89（1 microM）抑制PKA或用GF109203X（1 microM）抑制PKC，均可减弱VIP（1 nM）的作用。GF109203X（1 microM）可消除VPAC1激动剂[K15, R16, L27] VIP(1 - 7)/GRF(8 - 27)（10 nM）对海马突触传递的作用，但H - 89（1 microM）对此无影响。在同时存在PAC1和VPAC1拮抗剂M65（30 nM）和PG 97 - 269（100 nM）的情况下，RO 25 - 1553（100 nM）的作用被H - 89（1 microM）强烈抑制，但不受GF109203X（1 microM）影响。结论是，VIP通过激活VPAC1和VPAC2受体增强对CA1锥体神经元树突的突触传递。VPAC1介导的作用依赖于PKC活性，而VPAC2介导的作用则是VIP对海马CA1区传递的PKA依赖性作用的原因。