生物谷：继与人体冷知觉相关的基因“浮出水面”后，科学家最近又确定了第一个直接与肌体痒知觉相关的基因。这一发现有望为新型抗瘙痒药物的开发开辟新的道路。相关论文7月25日在线发表于《自然》杂志。
新发现的基因位于中央神经系统，它可以产生“胃泌素释放蛋白受体”（GRPR）。许多科学家都试图研究GRPR基因与疼痛知觉的相关性，并没有人将它与瘙痒联系起来。
在最新的研究中，由美国华盛顿大学医学院的华人遗传学家Zhou-Feng Chen领导的小组对GRPR基因进行了深入的研究。他们发现，GRPR仅存在于一些脊髓神经元中，而这些神经细胞能够将痛和痒的信号传递给大脑。进一步的研究表明，肌体产生疼痛知觉并不一定需要GRPR蛋白受体——失去GRPR基因的小鼠仍然能够对热量、炎症和机械伤害产生疼痛反应。
研究人员随后对GRPR基因突变的小鼠注射了组胺等痒诱导物质，从而确定了GRPR与痒知觉的相关性。他们发现，突变小鼠不会像正常小鼠一样到处乱挠。而当正常小鼠被注射仿GRPR蛋白功能的物质时，它们抓狂地更厉害了。
许多疾病，包括皮肤病和肿瘤都会引起慢性瘙痒，这是一项顽疾，而新的发现无疑将为瘙痒患者带来希望。
美国加州大学戴维斯分校的神经学家Earl Carstens和加拿大麦吉尔大学的遗传学家Jeffrey Mogil都对新的研究成果表示了赞赏，他们一致认为GRPR是一个“不同寻常的分子标靶”。（科学网 任霄鹏/编译）
原始出处:
Nature advance online publication 25 July 2007 | doi:10.1038/nature06029; Received 4 August 2006; Accepted 18 June 2007; Published online 25 July 2007
A gastrin-releasing peptide receptor mediates the itch sensation in the spinal cord
Yan-Gang Sun1 & Zhou-Feng Chen1,2,3
Department of Anesthesiology,
Department of Molecular Biology and Pharmacology,
Department of Psychiatry, Washington University School of Medicine Pain Center, St Louis, Missouri 63110, USA
Correspondence to: Zhou-Feng Chen1,2,3 Correspondence and requests for materials should be addressed to Z.F.C. (Email: chenz@wustl.edu).
Itching, or pruritus, is defined as an unpleasant cutaneous sensation that serves as a physiological self-protective mechanism to prevent the body from being hurt by harmful external agents. Chronic itch represents a significant clinical problem resulting from renal diseases and liver diseases, as well as several serious skin diseases such as atopic dermatitis1, 2, 3. The identity of the itch-specific mediator in the central nervous system, however, remains elusive. Here we describe that the gastrin-releasing peptide receptor (GRPR) plays an important part in mediating itch sensation in the dorsal spinal cord. We found that gastrin-releasing peptide is specifically expressed in a small subset of peptidergic dorsal root ganglion neurons, whereas expression of its receptor GRPR is restricted to lamina I of the dorsal spinal cord. GRPR mutant mice showed comparable thermal, mechanical, inflammatory and neuropathic pain responses relative to wild-type mice. In contrast, induction of scratching behaviour was significantly reduced in GRPR mutant mice in response to pruritogenic stimuli, whereas normal responses were evoked by painful stimuli. Moreover, direct spinal cerebrospinal fluid injection of a GRPR antagonist significantly inhibited scratching behaviour in three independent itch models. These data demonstrate that GRPR is required for mediating the itch sensation rather than pain, at the spinal level. Our results thus indicate that GRPR may represent the first molecule that is dedicated to mediating the itch sensation in the dorsal horn of the spinal cord, and thus may provide a central therapeutic target for antipruritic drug development.
