Laurent Patrick, Becker Jerome A J, Valverde Olga, Ledent Catherine, de Kerchove d'Exaerde Alban, Schiffmann Serge N, Maldonado Rafael, Vassart Gilbert, Parmentier Marc
Institut de Recherche Interdisciplinaire en Biologie Humaine et Moléculaire (I.R.I.B.H.M.), Université Libre de Bruxelles, Campus Erasme, Route de Lennik 808, Brussels, Belgium.
Nat Neurosci. 2005 Dec;8(12):1735-41. doi: 10.1038/nn1585. Epub 2005 Nov 20.
Prolactin-releasing peptide (PrRP) and its receptor G protein-coupled receptor 10 (GPR10) are expressed in brain areas involved in the processing of nociceptive signals. We investigated the role of this new neuropeptidergic system in GPR10-knockout mice. These mice had higher nociceptive thresholds and stronger stress-induced analgesia than wild-type mice, differences that were suppressed by naloxone treatment. In addition, potentiation of morphine-induced antinociception and reduction of morphine tolerance were observed in mutants. Intracerebroventricular administration of PrRP in wild-type mice promoted hyperalgesia and reversed morphine-induced antinociception. PrRP administration had no effect on GPR10-mutant mice, showing that its effects are mediated by GPR10. Anti-opioid effects of neuropeptide FF were found to require a functional PrRP-GPR10 system. Finally, GPR10 deficiency enhanced the acquisition of morphine-induced conditioned place preference and decreased the severity of naloxone-precipitated morphine withdrawal syndrome. Altogether, our data identify the PrRP-GPR10 system as a new and potent negative modulator of the opioid system.
催乳素释放肽（PrRP）及其受体G蛋白偶联受体10（GPR10）在参与伤害性信号处理的脑区中表达。我们在GPR10基因敲除小鼠中研究了这个新的神经肽系统的作用。这些小鼠比野生型小鼠具有更高的伤害性阈值和更强的应激诱导镇痛作用，纳洛酮处理可抑制这些差异。此外，在突变体中观察到吗啡诱导的镇痛作用增强以及吗啡耐受性降低。在野生型小鼠中脑室内注射PrRP可促进痛觉过敏并逆转吗啡诱导的镇痛作用。PrRP给药对GPR10突变小鼠没有影响，表明其作用是由GPR10介导的。发现神经肽FF的抗阿片样物质作用需要功能性的PrRP - GPR10系统。最后，GPR10缺乏增强了吗啡诱导的条件性位置偏爱反应的获得，并降低了纳洛酮诱发的吗啡戒断综合征的严重程度。总之，我们的数据确定PrRP - GPR10系统是阿片样物质系统新的强效负性调节因子。
