Evidence for activation of the tissue kallikrein-kinin system in nociceptive transmission and inflammatory responses of mice using a specific enzyme inhibitor
Jad. Emim et al., Evidence for activation of the tissue kallikrein-kinin system in nociceptive transmission and inflammatory responses of mice using a specific enzyme inhibitor, BR J PHARM, 130(5), 2000, pp. 1099-1107
1 The pharmacological activity of phenylacetyl-Phe-Ser-Arg-N-(2,4-dinitroph
enyl)-ethylenediamine (TKI), a tissue kallikrein specific inhibitor, was as
sessed using models of nociception and inflammation in mice.
2 Injection of TKI (13.6-136 mu mol kg(-1), i.p. or 41-410 mu mol kg(-1), s
.c.) produced a dose-related inhibition of the acetic acid-induced writhes
(by 37 to 85% or 34 to 80%, respectively). The antinociceptive activity of
TKI (41 mu mol kg(-1), i.p.) was maximal after 30 min injection and lasted
for 120 min. The effect was unaltered by pretreatment with naloxone (8.2 mu
mol kg(-1), s.c.) or bilateral adrenalectomy.
3 TRI (41 and 136 mu mol kg(-1), i.p.) produced a dose-related decrease of
the late phase of formalin-induced nociception by 79 and 98%, respectively.
At 136 mu mol kg(-1), i.p., TKI also shortened the duration of paw licking
in the early phase by 69%. TKI (41 and 136 mu mol kg(-1), i.p.) also reduc
ed the capsaicin-induced nociceptive response (by 51 to 79%).
4 TKI (41 pmol kg(-1), i.p. or 410 mu mol kg(-1), s.c.) reduced the oedemat
ogenic response, from the second to the fifth hour after carrageenin inject
ion by 36 to 30% or by 47 to 39%, respectively.
5 Pretreatment with TKI (41 mu mol kg(-1), i.p.) reduced the capsaicin-indu
ced neurogenic inflammation in the mouse ear by 54%.
6 It is concluded that TKI presents antinociceptive and antiinflammatory ac
tivities mediated by inhibition of kinin formation by tissue kallikrein in
mice. The results also indicate that the tissue kallikrein-dependent pathwa
y contributes to kinin generation in nociceptive and inflammatory processes
in mice.