kaolinite and icatibant

Effects of the angiotensin-converting enzyme (ACE) inhibitors, imidapril and enalapril, on kaolin-induced writhing reaction, which is believed to be caused by bradykinin (BK), were examined in mice. The number of writhes was increased significantly by 200 microg/kg of imidapril and by 100 and 200 microg/kg of enalapril. The intensity of writhing reaction was significantly suppressed by 1,000 nmol/kg of icatibant, a selective bradykinin B2 receptor antagonist, in the imidapril-, but not in the enalapril-treated groups. These results suggest that the potentiating effect of enalapril on kaolin-induced writhing reaction is greater than that of imidapril. This might depend on the difference of their inhibitory effects on BK degradation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Bradykinin Receptor Antagonists; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Enalapril; Imidazoles; Imidazolidines; Kaolin; Male; Mice; Mice, Inbred ICR; Pain

The daily variation in an intensity of kaolin-induced writhing reaction was examined in mice kept under conditions of light; 07:00 - 19:00 and dark; 19:00 - 07:00. The number of writhes was counted for 30 minutes after a single intraperitoneal injection of kaolin at 00:00, 02:00, 04:00, 06:00, 08:00, 10:00, 12:00, 14:00, 16:00, 18:00, 20:00 and 22:00. The number of writhes showed a daily variation with a peak at 18:00 and a trough at 06:00. The intensity of writhing reaction was significantly reduced by pretreatment with the bradykinin B1 (Des-Arg9-[Leu8]-BK) and B2 (icatibant) receptor antagonists. Significant daily variation in this parameter was still observed in the group with the B1 antagonist, but disappeared in the B2 antagonist-treated group. These results suggest that the kaolin-induced writhing reaction shows the daily variation with a peak at the end of the resting period and a trough at the end of the active period. The B2 receptor mediated stimuli appears to be involved in this phenomenon.

Topics: Analgesia; Animals; Bradykinin; Bradykinin Receptor Antagonists; Circadian Rhythm; Kaolin; Kinetics; Male; Mice; Mice, Inbred ICR; Pain; Photoperiod

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.

Topics: Acetates; Acetic Acid; Analgesics; Animals; Bradykinin; Dinoprostone; Female; Indomethacin; Injections, Intraperitoneal; Kaolin; Mice; Pain Measurement; Zymosan