Neuropeptide Y and peptide YY inhibit excitatory synaptic transmission in the rat dorsal motor nucleus of the vagus
Neuropeptide Y and peptide YY inhibit excitatory synaptic transmission in the rat dorsal motor nucleus of the vagus
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DOI：
10.1113/jphysiol.2003.042036
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发表时间：
2003-06-15
影响因子：
5.5
通讯作者：
Travagli, RA
中科院分区：
文献类型：
--
作者：
Browning, KN;Travagli, RA
胰多肽（PP）如神经肽Y（NPY）和肽YY（PYY）对胃肠（GI）运动和分泌发挥深刻的迷走神经介导的作用。全细胞膜片钳记录从脑干切片含有鉴定的GI投射大鼠迷走神经背侧运动核（DMV）神经元，以确定PP的作用机制。电刺激孤束核（NTS）诱导兴奋性突触后电流（EPSC），NPY和PYY（均在0.1-300 nm）在65%的神经元中以浓度依赖性方式降低。在没有突触后膜输入电阻或EPSC的上升和衰减时间的变化的配对脉冲比的增加表明，PPs对EPSC的影响是由于在突触前受体的行动。Y1和Y2受体选择性激动剂[Leu（31），Pro（34）]NPY和NPY（3-36）（均在100 nm处）模拟NPY和PYY对EPSC振幅的抑制。100 nm的NPY，但不是PYY的影响，部分拮抗Y1受体选择性拮抗剂BIBP 3226（0.1 μ m）。此外，用α 1肾上腺素能受体拮抗剂育亨宾（10 μ m）预处理可部分减弱NPY而非PYY诱导的EPSC振幅抑制，用α 2肾上腺素能受体激动剂UK 14，304（10 μ m）以及利血平预处理可部分阻断这种抑制。BIBF 3226和育亨宾联合预处理几乎完全拮抗了NPY介导的对EPSC的作用。与EPSC的抑制相反，PP灌注对抑制性突触后电流（IPSC）的振幅没有影响，对少数DMV神经元的影响很小。所用受体亚型和NPY和PYY作用机制的差异可能表明它们在背侧迷走神经复合体（DVC）回路中的作用存在功能差异。
Pancreatic polypeptides (PPs) such as neuropeptide Y (NPY) and peptide YY (PYY) exert profound, vagally mediated effects on gastrointestinal (GI) motility and secretion. Whole-cell patch clamp recordings were made from brainstem slices containing identified GI-projecting rat dorsal motor nucleus of the vagus (DMV) neurons to determine the mechanism of action of PPs. Electrical stimulation of nucleus tractus solitarii (NTS) induced excitatory postsynaptic currents (EPSCs) that were reduced in a concentration-dependent manner by NPY and PYY (both at 0.1-300 nm) in 65% of the neurons. An increase in the paired-pulse ratio without changes in the postsynaptic membrane input resistance or EPSC rise and decay time suggested that the effects of PPs on EPSCs were due to actions at presynaptic receptors. The Y1 and Y2 receptor selective agonists [Leu(31),Pro(34)]NPY and NPY(3-36) (both at 100 nm) mimicked the inhibition of NPY and PYY on the EPSC amplitude. The effects of 100 nm NPY, but not PYY, were antagonized partially by the Y1 receptor selective antagonist BIBP3226 (0.1 mum). In addition, the inhibition of the EPSC amplitude induced by NPY, but not PYY, was attenuated partially by pretreatment with the a, adrenoceptor antagonist yohimbine (10 mum), and occluded partially by the alpha(2) adrenoceptor agonist UK14,304 (10 am) as well as by pretreatment with reserpine. Pretreatment with a combination of BIBP3226 and yohimbine almost completely antagonized the NPY-mediated effects on EPSCs. Contrary to the inhibition of EPSCs, perfusion with PPs had no effect on the amplitude of inhibitory postsynaptic currents (IPSCs) and a minimal effect on a minority of DMV neurons. Differences in the receptor subtypes utilized and in the mechanism of action of NPY and PYY may indicate functional differences in their roles within the circuitry of the dorsal vagal complex (DVC).