Lv Shuang- Yu, Yang Yan Jie, Hong Shangyu, Wang Ning- Bo, Qin Yao- Jun, Li Wei- Xin, Chen Qiang
Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, 222 Tianshui South Road, Lanzhou, Gansu 730000, China.
Protein Pept Lett. 2013 Aug;20(8):926-31. doi: 10.2174/0929866511320080010.
Apelin was identified as natural ligand for APJ, a G protein-coupled receptor. APJ is expressed in spinal cord and dorsal root ganglion. This study was designed to investigate the effects and mechanisms of intrathecally (i.t.) administered apelin-13 on nociceptive response in formalin test and tail-flick test. In formalin test, i.t. injection of apelin-13 (0.3-3 nmol/mouse) had no effect on the nociceptive response in either acute phase (0-10 min) or interphase (10-20 min), but significantly produced hyperalgesic effect in late phase (20-30 min) at the dose of 3 nmol/mouse. The APJ receptor antagonist apelin-13(F13A) and GABAA receptor antagonist bicuculline methiodide, but not opioid receptor antagonist naloxone, significantly blocked the hyperalgesia caused by apelin-13 in late phase, indicating that i.t. apelin-13- induced hyperalgesia was mediated by APJ and GABAA receptor, rather than opioid receptor. However, in tail-flick test, i.t. injected apelin-13 (1 and 3 nmol/mouse) induced a significant antinociceptive effect, which was significantly antagonized by apelin-13(F13A) and naloxone, suggesting APJ and opioid receptor were involved in the antinociception of spinal apelin-13.
Apelin被确定为G蛋白偶联受体APJ的天然配体。APJ在脊髓和背根神经节中表达。本研究旨在探讨鞘内注射apelin-13对福尔马林试验和甩尾试验中伤害性反应的影响及机制。在福尔马林试验中，鞘内注射apelin-13（0.3 - 3 nmol/只小鼠）对急性期（0 - 10分钟）或间期（10 - 20分钟）的伤害性反应无影响，但在3 nmol/只小鼠剂量下，在后期（20 - 30分钟）显著产生痛觉过敏效应。APJ受体拮抗剂apelin-13(F13A)和GABAA受体拮抗剂甲磺酸荷包牡丹碱可显著阻断apelin-13在后期引起的痛觉过敏，而阿片受体拮抗剂纳洛酮则不能，这表明鞘内注射apelin-13诱导的痛觉过敏是由APJ和GABAA受体介导的，而非阿片受体。然而，在甩尾试验中，鞘内注射apelin-13（1和3 nmol/只小鼠）诱导出显著的镇痛作用，apelin-13(F13A)和纳洛酮可显著拮抗该作用，提示APJ和阿片受体参与了脊髓apelin-直的镇痛作用。
