Glass Michael J, Chan June, Pickel Virginia M
Department of Neurology and Neuroscience, Division of Neurobiology, Weill Medical College of Cornell University, New York, New York 10021, USA.
J Neurosci Res. 2002 Mar 15;67(6):753-65. doi: 10.1002/jnr.10185.
Neuropeptide Y (NPY) Y1 receptor (Y1-R) agonists influence cardiovascular regulation. These actions may involve NPY- and catecholamine-containing neurons in the medial nucleus of the solitary tract (mNTS), at the level of the area postrema. The cellular sites through which Y1-R agonists may interact with NPY and catecholamines in the mNTS, however, are not known. To determine potential sites of action for Y1-R agonists, and their relationship to NPY or catecholamines in the mNTS, we used electron microscopic immunocytochemistry for the detection of sequence-specific antipeptide antisera against Y1-R alone or in combination with antisera against NPY or the catecholamine-synthesizing enzyme tyrosine hydroxylase (TH). Analyses were conducted in the rat mNTS, at the level of the area postrema. Y1-R was found mainly in small unmyelinated axons and axon terminals but also in some somata and dendrites as well as a small number of glia. Within axon terminals, labeling for Y1-R was often present on dense core vesicles and small synaptic vesicles as well as extrasynaptic areas of the plasmalemma. Some Y1-R-labeled terminals also contained NPY or TH, suggesting that agonists of Y1-R may influence the release of NPY or catecholamines in the mNTS. In addition, Y1-R was found in dendrites that received asymmetric excitatory-type synapses from unlabeled axon terminals. Some of these dendrites contained NPY or TH, which indicates that Y1-R may be targeted for functional activation within NPY- or catecholamine-expressing neurons in the mNTS. These results demonstrate that Y1-R is a presynaptic receptor in NPY- or catecholamine-containing axon terminals within the mNTS as well as a postsynaptic receptor on NPY- or catecholamine-containing neurons that are contacted by axon terminals that likely contain excitatory amino acid transmitters. Agonists of Y1-R in the mNTS may thus affect cardiovascular regulation by modulating NPY, catecholamine, and excitatory amino acid transmission.
神经肽Y（NPY）Y1受体（Y1-R）激动剂会影响心血管调节。这些作用可能涉及孤束核内侧核（mNTS）中含NPY和儿茶酚胺的神经元，位于最后区水平。然而，Y1-R激动剂可能在mNTS中与NPY和儿茶酚胺相互作用的细胞位点尚不清楚。为了确定Y1-R激动剂的潜在作用位点，以及它们与mNTS中NPY或儿茶酚胺的关系，我们使用电子显微镜免疫细胞化学来检测针对Y1-R的序列特异性抗肽抗血清，单独或与针对NPY或儿茶酚胺合成酶酪氨酸羟化酶（TH）的抗血清联合使用。分析在大鼠mNTS中最后区水平进行。发现Y1-R主要存在于无髓小轴突和轴突终末，但也存在于一些胞体和树突以及少量神经胶质细胞中。在轴突终末内，Y1-R的标记常常出现在致密核心囊泡、小突触囊泡以及质膜的突触外区域。一些Y1-R标记的终末也含有NPY或TH，这表明Y1-R激动剂可能影响mNTS中NPY或儿茶酚胺的释放。此外，在接受来自未标记轴突终末的不对称兴奋性突触的树突中发现了Yl-R。其中一些树突含有NPY或TH，这表明Y1-R可能是mNTS中表达NPY或儿茶酚胺的神经元内功能激活的靶点。这些结果表明，Y1-R是mNTS中含NPY或儿茶酚胺的轴突终末中的突触前受体，也是含NPY或儿茶酚胺的神经元上的突触后受体，这些神经元与可能含有兴奋性氨基酸递质的轴突终末接触。因此，mNTS中Y1-R的激动剂可能通过调节NPY、儿茶酚胺和兴奋性氨基酸传递来影响心血管调节。
