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


METHODS
Scratching was induced by an intradermal (i.d.) injection of trypsin or the selective PAR-2 activating peptide SLIGRL-NH(2) at the back of the mouse neck. The animals were observed for 40 min and their scratching response was quantified.


RESULTS
I.d. injection of trypsin or SLIGRL-NH(2) 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-NH(2). 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-NH(2). 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-NH(2)-induced scratching behaviour when injected by i.d. or intrathecal (i.t.) routes. Also, the response to SLIGRL-NH(2) was inhibited by i.t. (but not by i.d.) treatment with DALBK. Conversely, neither Hoe 140 nor DALBK were able to inhibit SLIGRL-NH(2)-induced scratching behaviour when given intracerebroventricularly (i.c.v.).


CONCLUSIONS
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.
Costa
Robson
R
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
Manjavachi
Marianne N
MN
Motta
Emerson M
EM
Marotta
Denise M
DM
Juliano
Luiz
L
Torres
Hugo A
HA
Pesquero
João B
JB
Calixto
João B
JB
D000818:Animals; D000982:Antipruritics / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D004149:Dioxoles / Q000008:administration & dosage; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007271:Injections, Intradermal; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009842:Oligopeptides / Q000008:administration & dosage; D017288:Pain Threshold; D011537:Pruritus / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control / Q000523:psychology; D011804:Quinolines / Q000008:administration & dosage; D043783:Receptor, Bradykinin B1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D044464:Receptor, PAR-2 / Q000819:agonists / Q000378:metabolism*; D013449:Sulfonamides / Q000008:administration & dosage; D014357:Trypsin / Q000008:administration & dosage
C487113:2-((3-(1,3-benzodioxol-5-yl)-3-(((6-methoxy-2-naphthyl)sulfonyl)amino)propanoyl)amino)-3-(4-((2,6-dimethylpiperidinyl)methyl)phenyl)-N-isopropyl-N-methylpropanamide; D000982:Antipruritics; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D004149:Dioxoles; C105311:FR 173657; D009842:Oligopeptides; D011804:Quinolines; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D044464:Receptor, PAR-2; D013449:Sulfonamides; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; C051090:bradykinin, Leu(8)-des-Arg(9)-; C065679:icatibant; D014357:Trypsin; D001920:Bradykinin