DIFFERENTIAL SENSITIVITY OF ANTINOCICEPTIVE ASSAYS TO THE BRADYKININ ANTAGONIST HOE-140

1 The antinociceptive activity of the bradykinin (BK) BK2 receptor antagonist D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]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 mug BK/mouse, and 1 mug BK/mouse in mice pre-sensitized by i.p injection of prostaglandin E2 (PGE2). The ED50 values in these assays were 1.9 and 3.7 mug 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. ED25 values in these assays were 2.7 and 16.1 mug 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.