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Participation of peripheral P2Y(1), P2Y(6) and P2Y(11) receptors in formalin-induced inflammatory pain in rats

机译:周围P2Y(1),P2Y(6)和P2Y(11)受体参与福尔马林诱发的大鼠炎症性疼痛

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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.
机译: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,已在感觉神经系统中描述了P2Y(1),P2Y(6)和P2Y(11)受体,但对它们在行为痛觉模型中在外周水平的参与却知之甚少。这项研究评估了外围P2Y(1),P2Y(6)和P2Y(11)受体在福尔马林诱发的炎症性疼痛中的作用。用内源性P2Y(1)(ADP,100-1000 nmol / paw),P2Y(6)(UDP,180-300 nmol / paw)和P2Y(11)(ATP,100 -1000 nmol / paw)或选择性P2Y(1)(MRS2365,0.1-10 nmol / paw),P2Y(6)(PS130474,0.1-0.10 pmol / paw)和P2Y(11)(NF546,0.3-3 nmol /爪)受体激动剂可增加0.5%福尔马林诱导的退缩行为。相应地,使用选择性P2Y(1)(MRS2500,0.01-10 pmol / paw),P2Y(6)(MRS2578,3-30 nmol / paw)和P2Y(11)(NF340,1-10 nmol)进行外围预处理/爪)受体拮抗剂可显着降低1%福尔马林诱导的退缩行为。此外,ADP(100 nmol / paw)或MRS2365(10 nmol / paw),UDP(300 nmol / paw)或PSB0474(10 pmol / paw)和ATP(1000 nmol / paw)或NF546(3 nmol)的伤害感受/ paw)被选择性P2Y(1)(MRS2500,0.01 nmol / paw),P2Y(6)(MRS2578,3 nmol / paw)和P2Y(11)(NF340,1 nmol / paw)受体拮抗剂阻断,分别。 Western印迹分析证实背根神经节(DRG)和坐骨神经中存在P2Y(1)(66 kDa),P2Y(6)(36 kDa)和P2Y(11)(75 kDa)受体。结果表明,P2Y(1),P2Y(6)和P2Y(11)受体的外周激活在福尔马林引起的疼痛中起着伤害感受的作用。 (C)2014 Elsevier Inc.保留所有权利。

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