Goldenberg M M, Subers E M
Life Sci. 1983 Nov 21;33(21):2121-7. doi: 10.1016/0024-3205(83)90336-3.
The effect of synthetic leukotriene D4 (LTD4) was evaluated on isolated gastric longitudinal or circular smooth muscle and distal colon of the rat. The concentrations of LTD4, 2.5 X 10(-10)M to 5 X 10(-7)M, evoked minimal to maximal contractile responses. In addition, selected prostaglandins were used to identify the mediator of LTD4-induced contraction of gastric smooth muscle. FPL 55712 inhibited LTD4-induced contractions of gastric longitudinal or circular muscle. Indomethacin inhibited only LTD4-induced contractions of the longitudinal muscle. A combination of FPL 55712 and indomethacin produced greater inhibition of LTD4-induced contractions of longitudinal muscle than either agent alone. However, the same combination of inhibitors showed no greater effect than FPL 55712 alone on LTD4-induced contractions of circular smooth muscle. Unlike PGI2, PGF2, PGA2, or PGD2, PGE2 evoked contraction of the longitudinal muscle and relaxation of the circular muscle of the stomach. The dissimilar effect of PGE2 in the two smooth muscle layers of the rat stomach may signify that PGE2 is the prostaglandin released by LTD4 from the longitudinal and circular gastric muscle. However, the opposing pharmacologic effects following LTD4-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, PGE2 and other prostaglandins contract gastric longitudinal muscle in response to LTD4. Thus, these studies clearly suggest that LTD4 has both a direct and indirect effect on gastric smooth muscle of the rat. Unlike the stomach, LTD4-induced contraction of the distal colon was not inhibited by indomethacin while FPL 55712 antagonized contractions. Thus, these findings indicate a differential mechanism of stimulation of rat gastrointestinal tissue by LTD4.
评估了合成白三烯D4（LTD4）对大鼠离体胃纵行或环行平滑肌以及远端结肠的作用。LTD4浓度为2.5×10⁻¹⁰M至5×10⁻⁷M时，可引起最小至最大的收缩反应。此外，选用了一些前列腺素以确定LTD4诱导胃平滑肌收缩的介质。FPL 55712可抑制LTD4诱导的胃纵行或环行肌收缩。吲哚美辛仅抑制LTD4诱导的纵行肌收缩。FPL 55712与吲哚美辛联合使用对LTD4诱导的纵行肌收缩的抑制作用比单独使用任何一种药物都更强。然而，相同的抑制剂组合对LTD4诱导的环行平滑肌收缩的作用并不比单独使用FPL 55712更强。与前列环素I2（PGI2）、前列腺素F2α（PGF2）、前列腺素A2（PGA2）或前列腺素D2（PGD2）不同，前列腺素E2（PGE2）可引起胃纵行肌收缩和环行肌舒张。PGE2在大鼠胃的两层平滑肌中的不同作用可能表明PGE2是LTD4从胃纵行和环行肌释放的前列腺素。然而，LTD4诱导前列腺素在胃环行肌中释放后产生的相反药理作用会使吲哚美辛在该组织中无法表现出抑制作用。相比之下，PGE2和其他前列腺素会响应LTD4而使胃纵行肌收缩。因此，这些研究清楚地表明LTD4对大鼠胃平滑肌既有直接作用又有间接作用。与胃不同，LTD4诱导的远端结肠收缩不受吲哚美辛抑制，而FPL 55712可拮抗收缩。因此，这些发现表明LTD4刺激大鼠胃肠道组织的机制存在差异。
