Modulation of inhibitory neurotransmission in brainstem vagal circuits by NPY and PYY is controlled by cAMP levels.
Modulation of inhibitory neurotransmission in brainstem vagal circuits by NPY and PYY is controlled by cAMP levels.
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DOI：
10.1111/j.1365-2982.2009.01367.x
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发表时间：
2009-12
影响因子：
3.5
通讯作者：
Travagli RA
中科院分区：
文献类型：
--
作者：
Browning KN;Travagli RA
神经肽 Y (NPY) 和肽 YY (PYY) 等胰腺多肽对胃肠道 (GI) 运动发挥深远的迷走神经介导作用。迷走神经传出胃肠道的流量主要由迷走神经背侧运动核 (DMV) 神经元的强直 GABA 能突触输入决定，但两种肽均不调节 GABA 能传递。我们最近发现，由于静息 cAMP 水平较低，阿片类肽似乎同样无效。利用已识别的 DMV 神经元的全细胞记录，我们的目的是将脑干 cAMP 水平的影响与胰腺多肽调节 GABA 突触传递的能力联系起来。 NPY、PYY 或 Y1 或 Y2 受体选择性激动剂 [Leu,Pro]NPY 或 NPY(3-36) 均不会抑制诱发抑制性突触后电流 (eIPSC) 振幅，除非毛喉素或 8-溴-cAMP 通过暴露于腺苷酸环化酶偶联调节剂（例如胆囊收缩素八肽（硫酸化））来升高 cAMP 水平(CCK-8s) 或促甲状腺素释放激素 (TRH)，或通过迷走神经传入神经阻滞。 cAMP 水平初始增加后，[Leu,Pro]NPY 或 NPY(3-36) 对 eIPSC 振幅的抑制稳定约 30 分钟。此后，抑制作用逐渐下降，直至60分钟后激动剂再次无效。对自发电流和微型电流的分析表明，这种抑制作用是由于突触前 Y1 和 Y2 受体的作用所致。这些结果表明，与阿片肽类似，胰多肽对 GABA 能传递的影响取决于胃抑制迷走神经回路内 cAMP 的水平。
Pancreatic polypeptides such as neuropeptide Y (NPY) and peptide YY (PYY) exert profound, vagally mediated effects on gastrointestinal (GI) motility. Vagal efferent outflow to the GI tract is determined principally by tonic GABAergic synaptic inputs onto dorsal motor nucleus of the vagus (DMV) neurons, yet neither peptide modulates GABAergic transmission. We showed recently that opioid peptides appear similarly ineffective because of the low resting cAMP levels. Using whole cell recordings from identified DMV neurons, we aimed to correlate the influence of brainstem cAMP levels with the ability of pancreatic polypeptides to modulate GABAergic synaptic transmission. Neither NPY, PYY, nor the Y1 or Y2 receptor selective agonists [Leu,Pro]NPY or NPY(3–36) respectively, inhibited evoked inhibitory postsynaptic current (eIPSC) amplitude unless cAMP levels were elevated by forskolin or 8-bromo-cAMP, by exposure to adenylate cyclase-coupled modulators such as cholecystokinin octapeptide (sulfated) (CCK-8s) or thyrotropin releasing hormone (TRH), or by vagal deafferentation. The inhibition of eIPSC amplitude by [Leu,Pro]NPY or NPY(3–36) was stable for approximately 30 min following the initial increase in cAMP levels. Thereafter, the inhibition declined gradually until the agonists were again ineffective after 60 min. Analysis of spontaneous and miniature currents revealed that such inhibitory effects were due to actions at presynaptic Y1 and Y2 receptors. These results suggest that, similar to opioid peptides, the effects of pancreatic polypeptides on GABAergic transmission depend upon the levels of cAMP within gastric inhibitory vagal circuits.
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影响因子：
5.5
作者：
Browning, KN;Travagli, RA
通讯作者：
Travagli, RA
影响因子：
29.4
作者：
ADRIAN, TE;SAVAGE, AP;BLOOM, SR
通讯作者：
BLOOM, SR
影响因子：
5.3
作者：
Browning, KN;Kalyuzhny, AE;Travagli, RA
通讯作者：
Travagli, RA
影响因子：
2.5
作者：
Glatzer, Nicholas R.;Derbenev, Andrei V.;Smith, Bret N.
通讯作者：
Smith, Bret N.
DOI：
10.1111/j.1749-6632.1987.tb29477.x
发表时间：
1987-05-27
影响因子：
5.2
作者：
BARKER, JL;DUFY, B;VICINI, S
通讯作者：
VICINI, S