外周P2Y1、P2Y6和P2Y11受体在福尔马林诱导的大鼠炎性疼痛中的作用
Participation of peripheral P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain in rats.
作者信息
Barragán-Iglesias Paulino, Mendoza-Garcés Luis, Pineda-Farias Jorge Baruch, Solano-Olivares Verónica, Rodríguez-Silverio Juan, Flores-Murrieta Francisco Javier, Granados-Soto Vinicio, Rocha-González Héctor Isaac
机构信息
Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados (Cinvestav), Sede Sur. Calzada de los Tenorios 235, Col. Granjas Coapa, 14330 México, D.F., Mexico.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Col. Casco de Santo Tomas, Miguel Hidalgo, 11340 México, D.F., Mexico.
出版信息
Pharmacol Biochem Behav. 2015 Jan;128:23-32. doi: 10.1016/j.pbb.2014.11.001. Epub 2014 Nov 6.
Metabotropic P2Y receptors subfamily consists of eight functional mammalian receptors. Specifically, P2Y1, P2Y6 and P2Y11 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 P2Y1, P2Y6 and P2Y11 receptors in formalin-induced inflammatory pain. Ipsilateral, but not contralateral peripheral pre-treatment with the endogenous P2Y1 (ADP, 100-1000nmol/paw), P2Y6 (UDP, 180-300nmol/paw) and P2Y11 (ATP, 100-1000nmol/paw), or selective P2Y1 (MRS2365, 0.1-10nmol/paw), P2Y6 (PSB0474, 0.1-0.10pmol/paw) and P2Y11 (NF546, 0.3-3nmol/paw) receptor agonists increased 0.5% formalin-induced flinching behavior. Concordantly, peripheral pre-treatment with the selective P2Y1 (MRS2500, 0.01-10pmol/paw), P2Y6 (MRS2578, 3-30nmol/paw) and P2Y11 (NF340, 1-10nmol/paw) receptor antagonists significantly decreased 1% formalin-induced flinching behavior. Furthermore, the pronociceptive effect of ADP (100nmol/paw) or MRS2365 (10nmol/paw), UDP (300nmol/paw) or PSB0474 (10pmol/paw) and ATP (1000nmol/paw) or NF546 (3nmol/paw) was blocked by the selective P2Y1 (MRS2500, 0.01nmol/paw), P2Y6 (MRS2578, 3nmol/paw), and P2Y11 (NF340, 1nmol/paw) receptor antagonists, respectively. Western blot analysis confirmed the presence of P2Y1 (66kDa), P2Y6 (36kDa) and P2Y11 (75kDa) receptors in dorsal root ganglia (DRG) and sciatic nerve. Results suggest that peripheral activation of P2Y1, P2Y6 and P2Y11 receptors plays a pronociceptive role in formalin-induced pain.
代谢型P2Y受体亚家族由八个功能性哺乳动物受体组成。具体而言，P2Y1、P2Y6和P2Y11受体已在感觉神经系统中被描述，但其在外周水平参与行为性疼痛模型的情况却鲜为人知。本研究评估了外周P2Y1、P2Y6和P2Y11受体在福尔马林诱导的炎性疼痛中的作用。用内源性P2Y1（ADP，100 - 1000nmol/爪）、P2Y6（UDP，180 - 300nmol/爪）和P2Y11（ATP，100 - 1000nmol/爪），或选择性P2Y1（MRS2365，0.1 - 10nmol/爪）、P2Y6（PSB0474，0.1 - 0.10pmol/爪）和P2Y11（NF546，0.3 - 3nmol/爪）受体激动剂对外周进行同侧而非对侧预处理，可增加0.5%福尔马林诱导的退缩行为。与此一致的是，用选择性P2Y1（MRS2500，0.01 - 10pmol/爪）、P2Y6（MRS2578，3 - 30nmol/爪）和P2Y11（NF340，1 - 10nmol/爪）受体拮抗剂对外周进行预处理，可显著降低1%福尔马林诱导的退缩行为。此外，ADP（100nmol/爪）或MRS2365（10nmol/爪）、UDP（300nmol/爪）或PSB0474（10pmol/爪）以及ATP（1000nmol/爪）或NF546（3nmol/爪）的促痛作用分别被选择性P2Y1（MRS2500，0.01nmol/爪）、P2Y6（MRS2578，3nmol/爪）和P2Y11（NF340，1nmol/爪）受体拮抗剂所阻断。蛋白质印迹分析证实背根神经节（DRG）和坐骨神经中存在P2Y1（66kDa）、P2Y6（36kDa）和P2Y11（75kDa）受体。结果表明，P2Y1、P2Y6和P2Y11受体的外周激活在福尔马林诱导的疼痛中起促痛作用。
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