Lu Xiaoying, Mazarati Andrey, Sanna Pietro, Shinmei Steve, Bartfai Tamas
Department of Neuropharmacology, The Harold L. Dorris Neurological Research Center, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Neuropeptides. 2005 Jun;39(3):147-52. doi: 10.1016/j.npep.2004.12.011. Epub 2005 Jan 26.
Galanin, acting at the GalR1-3 subtypes of galanin receptors, is involved in the regulation of cognition, mood, feeding, seizure activity and pain. The understanding of galanin's effects in molecular and cellular terms has been hampered by the lack of receptor subtype selective ligands and antibodies. Previous in situ hybridization data showed that GalR1 and GalR2 receptors are abundant in the rat brain, while the distribution of GalR3 is contradictory and most studies demonstrated a low expression levels in the rat brain. The distribution of galanin receptor subtypes at protein level is unknown. In the present study, we report the regional distribution of the galanin receptors: GalR1 and non-GalR1 receptors, using a recently synthesized high affinity GalR2/3 selective ligand, galanin (2-11), and galanin (1-29), as competitors, in saturating (125)I-galanin membrane binding assay. We show that paraventricular nucleus (PVN) express predominantly GalR1, whereas areas like the dorsal raphe nucleus (DRN), hippocampus and amygdala express both the GalR1 and non-GalR1 receptors. We speculate that the GalR2/3 binding sites detected by galanin (2-11) binding in our study probably represent mostly GalR2 receptors. In addition, we show regionally specific and subtype specific regulation of galanin receptors. Status epilepticus (SE), known to deplete galanin from axonal projections of locus coeruleus and septum/diagonal band neurons in the hippocampus and to induce galanin expression in a subset of hippocampal cells, down regulates GalR2 receptor mRNA and proteins by 30% without altering the GalR1 receptors.
甘丙肽通过作用于甘丙肽受体的GalR1 - 3亚型，参与认知、情绪、进食、癫痫活动和疼痛的调节。由于缺乏受体亚型选择性配体和抗体，对甘丙肽在分子和细胞层面作用的理解受到了阻碍。先前的原位杂交数据显示，GalR1和GalR2受体在大鼠脑中含量丰富，而GalR3的分布则存在矛盾，大多数研究表明其在大鼠脑中表达水平较低。甘丙肽受体亚型在蛋白质水平的分布尚不清楚。在本研究中，我们在饱和的（125）I - 甘丙肽膜结合试验中，使用最近合成的高亲和力GalR2 / 3选择性配体甘丙肽（2 - 11）和甘丙肽（1 - 29）作为竞争者，报告了甘丙肽受体：GalR1和非GalR1受体的区域分布。我们发现室旁核（PVN）主要表达GalR1，而诸如中缝背核（DRN）、海马体和杏仁核等区域同时表达GalR1和非GalR1受体。我们推测，在我们的研究中通过甘丙肽（2 - 11）结合检测到的GalR2 / 3结合位点可能主要代表GalR2受体。此外，我们还展示了甘丙肽受体的区域特异性和亚型特异性调节。癫痫持续状态（SE）已知会使海马体中蓝斑和隔区/斜角带神经元的轴突投射中的甘丙肽耗竭，并在一部分海马体细胞中诱导甘丙肽表达，它会使GalR2受体的mRNA和蛋白质下调30%，而不会改变GalR1受体。
