Summary
Bradykinin (BK) produced a dose-related increase in the paw volume of the rat. Responses to BK at all doses used were not affected by pretreating the rats with diphenhydramine, 1 mg kg−1, or indomethacin, 2.5 and 5 mg kg−1. Indomethacin, 10 mg kg−1 produced a small but significant reduction in the responses to BK. Captopril 1 mg kg−1 enhanced responses to low but not to high doses of BK.
The rank order of potency of various kinin analogues to increase paw volume was found to be methionyl-lysyl-BK (met-lys-BK) > BK > kysyl-BK (Kallidin) ≫ des-Arg9-BK. The B1-receptor antagonist des-Arg9-Leu8-BK did not affect responses to BK on paw volume.
Two modified kinin fragments S2302 (H-D-Pro-Phe-Arg-p-Nitroaniline) and S2441 (H-D-Pro-Phe-Arg-NH-heptyl) produced dose-related increases in paw volume both having approximately half the potency of BK. These responses were not anagonised by diphenhydramine, 1 mg kg−1 which reduced significantly the response to histamine.
On the isolated rat uterus the rank order of potency of various kinins was BK > Kallidin > met-lys-BK > des-Arg9-BK. The two modified kinin fragments S2302 and S2441 (but not des-Arg9-Leu8-BK) antagonised BK induced contractions of the rat uterus.
From the rank order of potency studies the receptor mediating contraction of the rat uterus in vitro and increase in rat paw volume to BK appear to be of the same type. Whether the differences in the action of S2302 and S2441 in the rat paw and rat uterus reflect a real difference in receptor type requires further study.
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Whalley, E.T., Sampaio, C.A.M., Fritz, H. et al. The effect of kinins on paw oedema and uterus in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 328, 202–206 (1984). https://doi.org/10.1007/BF00512073
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DOI: https://doi.org/10.1007/BF00512073