Comparison of the effects of leukotrienes B4 and D4 on distal colonic motility in the rabbit in vivo

Abstract

Leukotrienes (LTs) have been shown to contract smooth muscle of the small and large intestine in vitro, and an increased mucosal synthesis of leukotrienes has been reported to occur in ulcerative colitis. The purpose of this study was to evaluate the effects of LTs B4 and D4 on the myoelectric and mechanical activity of the rabbit distal colon in vivo and to determine how these effects were modified by indomethacin. LTB4 had a weak excitatory action on both electrical and mechanical activity but this was not statistically significant; LTD4 on the other hand caused a significant dose-related increase in spike potential frequency and contractile activity. Indomethacin alone (1 mg/kg) had no significant effect on the electrical or mechanical activity of the colon but blocked the effects of subsequently administered LTD4. It is concluded from these data that at least part of the excitatory action of LTD4 results from its causing the synthesis and release of excitatory prostaglandins. However, whereas leukotrienes have the potential to play an important role in modulating colonic motility, it seems most likely that this effect would occur after pathological stimulus rather than in the normal healthy colon.