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 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 B₂receptor antagonists SSR240612 and {"type":"entrez-nucleotide","attrs":{"text":"FR173657","term_id":"257935500","term_text":"FR173657"}}FR173657, respectively, prevented the scratching behaviour caused by trypsin or SLIGRL-NH₂. Nonetheless, only treatment i.p. with the peptide B₂receptor antagonist, Hoe 140, but not the B₁receptor 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.