The role of kinin B1 and B2 receptors in the scratching behaviour induced by proteinase-activated receptor-2 agonists in mice
The role of kinin B1 and B2 receptors in the scratching behaviour induced by proteinase-activated receptor-2 agonists in mice
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DOI：
10.1111/j.1476-5381.2009.00571.x
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发表时间：
2010-02-01
影响因子：
7.3
通讯作者：
Calixto, Joao B.
中科院分区：
文献类型：
--
作者：
Costa, Robson;Manjavachi, Marianne N.;Calixto, Joao B.
背景与目的：蛋白酶激活受体2（PAR-2）的激活诱导小鼠抓挠行为。在这里，我们研究了激肽 B-1 和 B-2 受体在 PAR-2 激活剂引起的瘙痒反应中的作用。实验方法：通过在小鼠颈后皮内 (i.d.) 注射胰蛋白酶或选择性 PAR-2 激活肽 SLIGRL-NH2 来诱导抓挠。观察动物 40 分钟，并对它们的抓挠反应进行量化。 主要结果：同上。注射胰蛋白酶或 SLIGRL-NH2 会引起抓挠行为，这取决于 PAR-2 的激活。遗传上缺乏激肽 B-1 或 B-2 受体的小鼠在注射后表现出抓挠行为减少。注射胰蛋白酶或 SLIGRL-NH2。分别用非肽 B-1 或 B-2 受体拮抗剂 SSR240612 和 FR173657 进行治疗（腹腔注射），可防止胰蛋白酶或 SLIGRL-NH2 引起的抓挠行为。尽管如此，仅进行腹腔注射治疗。与肽 B-2 受体拮抗剂 Hoe 140（而非 B-1 受体拮抗剂 (DALBK)）一起使用，可抑制胰蛋白酶的致痒反应。当通过 i.d. 注射时，Hoe 140 也能有效对抗 SLIGRL-NH2 引起的抓伤行为。或鞘内 (i.t.) 途径。此外，对 SLIGRL-NH2 的反应也被 i.t. 抑制。 （但不是通过 i.d.）用 DALBK 治疗。相反，脑室内 (i.c.v.) 给药时，Hoe 140 和 DALBK 均不能抑制 SLIGRL-NH2 诱导的抓挠行为。 结论和意义：目前的结果表明，作用于 B-1 和 B-2 受体的激肽在控制小鼠 PAR-2 激活触发的瘙痒信号传导中发挥着至关重要的作用。
Background and purpose:Activation of the proteinase-activated receptor-2 (PAR-2) induces scratching behaviour in mice. Here, we have investigated the role of kinin B-1 and B-2 receptors in the pruritogenic response elicited by activators of PAR-2.Experimental approach:Scratching was induced by an intradermal (i.d.) injection of trypsin or the selective PAR-2 activating peptide SLIGRL-NH2 at the back of the mouse neck. The animals were observed for 40 min and their scratching response was quantified.Key results:I.d. injection of trypsin or SLIGRL-NH2 evoked a scratching behaviour, dependent on PAR-2 activation. Mice genetically deficient in kinin B-1 or B-2 receptors exhibited reduced scratching behaviour after i.d. injection of trypsin or SLIGRL-NH2. Treatment (i.p.) with the non-peptide B-1 or B-2 receptor antagonists SSR240612 and FR173657, respectively, prevented the scratching behaviour caused by trypsin or SLIGRL-NH2. Nonetheless, only treatment i.p. with the peptide B-2 receptor antagonist, Hoe 140, but not the B-1 receptor antagonist (DALBK), inhibited the pruritogenic response to trypsin. Hoe 140 was also effective against SLIGRL-NH2-induced scratching behaviour when injected by i.d. or intrathecal (i.t.) routes. Also, the response to SLIGRL-NH2 was inhibited by i.t. (but not by i.d.) treatment with DALBK. Conversely, neither Hoe 140 nor DALBK were able to inhibit SLIGRL-NH2-induced scratching behaviour when given intracerebroventricularly (i.c.v.).Conclusions and implications:The present results demonstrated that kinins acting on both B-1 and B-2 receptors played a crucial role in controlling the pruriceptive signalling triggered by PAR-2 activation in mice.