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 B1 and B2 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 B1 or B2 receptors exhibited reduced scratching behaviour after i.d. injection of trypsin or SLIGRL-NH2. Treatment (i.p.) with the non-peptide B1 or B2 receptor antagonists SSR240612 and FR173657, respectively, prevented the scratching behaviour caused by trypsin or SLIGRL-NH2. Nonetheless, only treatment i.p. with the peptide B2 receptor antagonist, Hoe 140, but not the B1 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 B1 and B2 receptors played a crucial role in controlling the pruriceptive signalling triggered by PAR-2 activation in mice.