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,Thi5D-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 micrograms BK/mouse, and 1 microgram 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 micrograms 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 micrograms 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.
Heapy
C G
CG
ICI Pharmaceuticals, Macclesfield, Cheshire.
Shaw
J S
JS
Farmer
S C
SC
D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015232:Dinoprostone / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D007616:Kaolin / Q000494:pharmacology; D051379:Mice; D010147:Pain Measurement; D015054:Zymosan / Q000494:pharmacology
D000085:Acetates; D000700:Analgesics; D007616:Kaolin; C065679:icatibant; D015054:Zymosan; D015232:Dinoprostone; D019342:Acetic Acid; D001920:Bradykinin; D007213:Indomethacin