The effect of leukotriene D 4 on the isolated stomach and colon of the rat

Abstract

The effect of synthetic leukotriene D 4 (LTD 4) was evaluated on isolated gastric longitudinal or circular smooth muscle and distal colon of the rat. The concentrations of LTD 4, 2.5 × 10 −10 M to 5 × 10 −7 M, evoked minimal to maximal contractile responses. In addition, selected prostaglandins were used to idetify the mediator of LTD 4-induced contraction of gastric smooth muscle. FPL 55712 inhibited LTD 4-induced contractions of gastric longitudinal or circular muscle. Indomethacin inhibited only LTD 4-induced contractions of the longitudinal muscle. A combination of FPL 55712 and indomethacin produced greater inhibition of LTD 4-induced contractions of longitudinal muscle than either agent alone. However, the same combination of inhibitors showed no greater effect than FPL 55712 alone on LTD 4-induced contractions of circular smooth muscle. Unlike PGI 2, PGF 2, PGA 2, or PGD 2, PGE 2 evoked contraction of the longitudinal muscle and relaxation of the circular muscle of the stomach. The dissimilar effect of PGE 2 in the two smooth muscle layers of the rat stomach may signify that PGE 2 is the prostaglandin released by LTD 4 from the longitudinal and circular gastric muscle. However, the opposing pharmacologic effects following LTD 4-induced release of prostaglandins in the circular muscle of the stomach would preclude the appearance of an inhibitory effect of indomethacin in this tissue. In contrast, PGE 2 and other prostaglandins contract gastric longitudinal muscle in response to LTD 4. Thus, these studies clearly suggest that LTD 4 has both a direct and indirect effect on gastric smooth muscle of the rat. Unlike the stomach, LTD 4-induced contraction of the distal colon was not inhibited by indomethacin while FPL 55712 antagonized contractions. Thus, these findings indicate a differential mechamism of stimulation of rat gastrointestinal tissue by LTD 4.