Primus R J, Yevich E, Gallager D W
Neurogen, 35 N.E. Industrial Rd., Branford, CT 06422, USA.
Brain Res Mol Brain Res. 1998 Jul 15;58(1-2):74-82. doi: 10.1016/s0169-328x(98)00083-7.
Guanylyl 5'-[gamma[35S]thio]-triphosphate (GTPgamma[35S]) binding to NPY receptor-activated G-proteins was measured in adult rat brain sections in order to determine the neuroanatomical distribution of NPY receptor subtypes. Using the pharmacological specificity of the NPY receptor subtypes, differential stimulation of GTPgamma[] binding by subtype-specific agonists was used to demonstrate the differential distribution of these subtypes in rat brain. Treatment of rat brain slices with selective agonists for the NPY receptor subtypes in the presence of 2000 microM GDP was used to discriminate populations of NPY receptor subtypes. Activation of a NPY Y1 receptor subtype by human [Leu31Pro34]NPY stimulated GTPgamma[35S] binding in the rank order: frontal cortex>dentate gyrus>inferior colliculus>/=thalamus>hypothalamus. In contrast, NPY Y2/Y5 peptide agonist, human PYY(3-36), stimulated GTPgamma[35S] binding in the rank order: hypothalamus>substantia nigra>hippocampus>frontal cortex>/=inferior colliculus. Stimulation of NPY Y5 receptor subtypes by a NPY Y5 selective agonist, rat/human D-Trp, was shown to stimulate GTPgamma[35S] binding in the hypothalamus and discrete nuclei of the thalamus. Little GTPgamma[35S] binding in the dentate gyrus, frontal cortex, or inferior colliculus was measured following stimulation with D-Trp. Stimulation of GTPgamma[35S] binding by [Leu31Pro34]NPY, but not by the other NPY receptor agonists, was blocked by the selective NPY Y1 receptor antagonist, BIBP 3226. In conclusion, functional coupling at NPY receptor subtypes can be shown in rat brain and populations of NPY receptor subtypes can be anatomically discriminated by NPY agonist stimulation of GTPgamma[35S] binding in rat brain.
为了确定神经肽Y（NPY）受体亚型的神经解剖学分布，我们检测了[γ-35S]硫代三磷酸鸟苷（GTPγ[35S]）与成年大鼠脑切片中NPY受体激活的G蛋白的结合情况。利用NPY受体亚型的药理学特异性，通过亚型特异性激动剂对GTPγ[35S]结合的差异刺激来证明这些亚型在大鼠脑中的差异分布。在2000微摩尔GDP存在的情况下，用NPY受体亚型的选择性激动剂处理大鼠脑切片，以区分NPY受体亚型群体。人[Leu31Pro34]NPY对NPY Y1受体亚型的激活刺激GTPγ[35S]结合的顺序为：额叶皮质>齿状回>下丘>/=丘脑>下丘脑。相比之下，NPY Y2/Y5肽激动剂人PYY(3-36)刺激GTPγ[35S]结合的顺序为：下丘脑>黑质>海马>额叶皮质>/=下丘。NPY Y5选择性激动剂大鼠/人D-Trp对NPY Y5受体亚型的刺激显示在下丘脑和丘脑的离散核中刺激GTPγ[35S]结合。用D-Trp刺激后，在齿状回、额叶皮质或下丘中未检测到GTPγ[35S]结合。[Leu31Pro34]NPY刺激GTPγ[35S]结合，但其他NPY受体激动剂则不能，这种刺激被选择性NPY Y1受体拮抗剂BIBP 3226阻断。总之，在大鼠脑中可以显示NPY受体亚型的功能偶联，并且通过NPY激动剂刺激大鼠脑中的GTPγ[35S]结合可以在解剖学上区分NPY受体亚型群体。
