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Differential sensitivity of antinociceptive assays to the bradykinin antagonist Hoe 140
Author(s) -
Heapy Christopher G.,
Shaw John S.,
Farmer Susannah C.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13464.x
Subject(s) - zymosan , bradykinin , antagonist , chemistry , ed50 , pharmacology , prostaglandin , prostaglandin d2 , endocrinology , receptor , biochemistry , medicine , in vitro
1 The antinociceptive activity of the bradykinin (BK) BK 2 receptor antagonist d ‐Arg‐[Hyp 3 ,Thi 5 , d ‐Tic 7 ,Oic 8 ]BK (Hoe 140) was determined in a range of mouse abdominal constriction assays. 2 Hoe 140 potently inhibited the response induced by i.p. injection of 10 μg BK/mouse, and 1 μg BK/mouse in mice pre‐sensitized by i.p injection of prostaglandin E 2 (PGE 2 ). The ED 50 values in these assays were 1.9 and 3.7 μg kg −1 respectively. This confirms that Hoe 140 is a potent antagonist of BK in vivo . 3 Hoe 140 produced potent, but incomplete inhibition of the responses evoked by i.p injection of kaolin or 0.25% acetic acid. ED 25 values in these assays were 2.7 and 16.1 μg kg −1 , and the maximum inhibition produced was 60% and 70% respectively. 4 At doses up to 1 mg kg −1 , Hoe 140 was completely ineffective against the abdominal constriction response induced by zymosan. In contrast, morphine, ibuprofen and indomethacin had similar potencies against zymosan, kaolin and acetic acid‐induced abdominal constriction. 5 Although zymosan, acetic acid and kaolin all produce qualitatively similar responses, it is appears that they achieve this by different mechanisms. The extent to which BK is involved as a mediator differs between the various types of abdominal constriction assay.