Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats
Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats
复制标题
DOI：
10.1016/j.pbb.2014.11.001
复制
发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Isaac Rocha-Gonzalez, Hector
中科院分区：
文献类型：
--
作者：
Barragan-Iglesias, Paulino;Mendoza-Garces, Luis;Isaac Rocha-Gonzalez, Hector
代谢型P2 Y受体亚家族由八种功能性哺乳动物受体组成。具体而言，P2 Y（1），P2 Y（6）和P2 Y（11）受体已被描述在感觉神经系统中，但他们的参与，在外周水平，在行为疼痛模型很少被理解。本研究评估外周P2 Y（1）、P2 Y（6）和P2 Y（11）受体在福尔马林诱导的炎性疼痛中的作用。内源性P2 Y对同侧外周进行预处理，但对侧未进行预处理（1）（ADP，100-1000 nmol/爪），P2 Y（6）（UDP，180-300 nmol/paw）和P2Y（11）（ATP，100-1000 nmol/paw）或选择性P2 Y（1）（MRS 2365，0.1-10 nmol/paw）、P2 Y（6）（PS130474，0.1-0.10 pmol/paw）和P2 Y（11）（NF 546，0.3-3 nmol/paw）受体激动剂增加0.5%福尔马林诱导的退缩行为。一致地，用选择性P2 Y（1）（MRS 2500，0.01-10 pmol/paw）、P2 Y（6）（MRS 2578，3-30 nmol/paw）和P2 Y（11）（NF 340，1-10 nmol/paw）受体拮抗剂的外周预处理显著降低1%福尔马林诱导的退缩行为。此外，ADP的原伤害性效应（100 nmol/爪）或MRS 2365（10 nmol/paw），UDP（300 nmol/爪）或PSB 0474（10 pmol/paw）和ATP（1000 nmol/爪）或NF 546（3 nmol/paw）分别被选择性P2 Y（1）（MRS 2500，0.01 nmol/paw）、P2 Y（6）（MRS 2578，3 nmol/paw）和P2 Y（11）（NF 340，1 nmol/paw）受体拮抗剂阻断。Western blot分析证实背根神经节（DRG）和坐骨神经中存在P2 Y（1）（66 kDa）、P2 Y（6）（36 kDa）和P2 Y（11）（75 kDa）受体。结果提示，外周P2 Y（1）、P2 Y（6）和P2 Y（11）受体的激活在福尔马林致痛中发挥了原伤害性感受作用。(C)2014爱思唯尔公司All rights reserved.
Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y(1), P2Y(6) and P2Y(11) receptors have been described in the sensory nervous system, but their participation, at peripheral level, in behavioral pain models is scarcely understood. This study assessed the role of peripheral P2Y(1), P2Y(6) and P2Y(11) receptors in formalin-induced inflammatory pain. Ipsilateral, but not contralateral peripheral pre-treatment with the endogenous P2Y(1) (ADP, 100-1000 nmol/paw), P2Y(6) (UDP, 180-300 nmol/paw) and P2Y(11) (ATP, 100-1000 nmol/paw), or selective P2Y(1) (MRS2365, 0.1-10 nmol/paw), P2Y(6) (PS130474, 0.1-0.10 pmol/paw) and P2Y(11) (NF546, 0.3-3 nmol/paw) receptor agonists increased 0.5% formalin-induced flinching behavior. Concordantly, peripheral pre-treatment with the selective P2Y(1) (MRS2500, 0.01-10 pmol/paw), P2Y(6) (MRS2578, 3-30 nmol/paw) and P2Y(11) (NF340, 1-10 nmol/paw) receptor antagonists significantly decreased 1% formalin-induced flinching behavior. Furthermore, the pronociceptive effect of ADP (100 nmol/paw) or MRS2365 (10 nmol/paw), UDP (300 nmol/paw) or PSB0474 (10 pmol/paw) and ATP (1000 nmol/paw) or NF546 (3 nmol/paw) was blocked by the selective P2Y(1) (MRS2500, 0.01 nmol/paw), P2Y(6) (MRS2578, 3 nmol/paw), and P2Y(11) (NF340, 1 nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y(1) (66 kDa), P2Y(6) (36 kDa) and P2Y(11) (75 kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y(1), P2Y(6) and P2Y(11) receptors plays a pronociceptive role in formalin-induced pain. (C) 2014 Elsevier Inc. All rights reserved.