Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is mediated by NMDA receptors.
Inhibition of food intake by PACAP in the hypothalamic ventromedial nuclei is mediated by NMDA receptors.
复制标题
DOI：
10.1016/j.physbeh.2014.05.029
复制
发表时间：
2014-06-22
影响因子：
2.9
通讯作者：
Choi S
中科院分区：
文献类型：
--
作者：
Resch JM;Maunze B;Phillips KA;Choi S
下丘脑腹内侧核（VMN）内注射腺苷酸环化酶激活多肽（PACAP）可产生依赖于PAC 1受体的食欲减退，但该受体下游的信号传导机制尚不清楚。尽管PACAP信号传导具有许多靶点，但已显示该神经肽通过涉及经由激活Src蛋白酪氨酸激酶家族的NMDA受体增强的机制影响几个脑区域中的谷氨酸信号传导。考虑到这一点，我们研究了Src-NMDA受体信号通路作为VMN中PACAP信号传导的靶点，其可能介导其对摄食行为的影响。在夜间进食条件下，NMDA受体拮抗剂之前，PACAP管理到VMN衰减PACAP介导的减少进食，表明通过NMDA受体的NMDA能信号是必要的PACAP诱导的食欲减退。此外，PACAP管理到VMN导致NMDA受体的GluN 2B亚基的酪氨酸磷酸化增加，Src激酶活性的抑制也阻断了PACAP管理到VMN对摄食行为的影响。这些结果表明，在VMN的PACAP神经传递可能会增强谷氨酸信号通过增强NMDA受体的活性，通过酪氨酸磷酸化事件介导的Src激酶家族，和NMDA受体活性的调制在下丘脑的PACAP可能是其调节食物摄入的主要机制。
Central injections of Pituitary adenylate cyclase-activating polypeptide (PACAP) into the ventromedial nuclei (VMN) of the hypothalamus produce hypophagia that is dependent upon the PAC1 receptor, however, the signaling downstream of this receptor in the VMN is unknown. Though PACAP signaling has many targets, this neuropeptide has been shown to influence glutamate signaling in several brain regions through mechanisms involving NMDA receptor potentiation via activation of the Src family of protein tyrosine kinases. With this in mind, we examined the Src-NMDA receptor signaling pathway as a target for PACAP signaling in the VMN that may mediate its effects on feeding behavior. Under nocturnal feeding conditions, NMDA receptor antagonism prior to PACAP administration into the VMN attenuated PACAP-mediated decreases in feeding suggesting glutamatergic signaling via NMDA receptors is necessary for PACAP-induced hypophagia. Furthermore, PACAP administration into the VMN resulted in increased tyrosine phosphorylation of the GluN2B subunit of the NMDA receptor, and inhibition of Src kinase activity also blocked the effects of PACAP administration into the VMN on feeding behavior. These results indicate that PACAP neurotransmission in the VMN likely augments glutamate signaling by potentiating NMDA receptors activity through tyrosine phosphorylation events mediated by the Src kinase family, and modulation of NMDA receptor activity by PACAP in the hypothalamus may be a primary mechanism for its regulation of food intake.
登录
查看更多内容
影响因子：
3.6
作者：
Engelund, Anna;Fahrenkrug, Jan;Hannibal, Jens
通讯作者：
Hannibal, Jens
影响因子：
2.5
作者：
Diamond, JS;Jahr, CE
通讯作者：
Jahr, CE
影响因子：
3.4
作者：
Borgland, S. L.;Storm, E.;Bonci, A.
通讯作者：
Bonci, A.
DOI：
10.1523/jneurosci.2721-12.2013
发表时间：
2013-02-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Chowdhury D;Marco S;Brooks IM;Zandueta A;Rao Y;Haucke V;Wesseling JF;Tavalin SJ;Pérez-Otaño I
通讯作者：
Pérez-Otaño I
影响因子：
8.1
作者：
Guyenet, Stephan J.;Matsen, Miles E.;Schwartz, Michael W.
通讯作者：
Schwartz, Michael W.