The role of kinin B1 and B2 receptors in the scratching behaviour induced by proteinase-activated receptor-2 agonists in mice

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.