Cysteinyl leucotriene receptor type 1 mediates contraction in human and guinea-pig oesophagus

Leucotriene D-4 (LTD4) causes contraction of the guinea-pig and cat oesophagus. Effects of cysteinyl leucotrienes in the human oesophagus were unknown. To investigate and compare the cysteinyl leucotriene effects in the human oesophagus with those in the guinea-pig oesophagus, we measured contraction of muscularis mucosae strips isolated from the human and guinea-pig oesophagus caused by cysteinyl leucotrienes, LTC4, LTD4 and LTE4, as well as the dihydroxy leucotriene, LTB4. Effects of leucotrienes in human were similar to those in guinea-pig oesophagus. LTC4 and LTD4 caused moderate, whereas LTE4 caused mild, concentration-dependent contraction. LTE4 was a partial agonist. In contrast, LTB4 did not cause any contraction. The relative potencies for cysteinyl leucotrienes to cause contraction were LTD4 = LTC4 > LTE4. The LTD4-induced contraction was moderately inhibited by two selective CysLT(1) receptor antagonists, montelukast and zafirlukast, in both human and guinea-pig oesophagus. In addition, the LTD4-induced contraction was not and only slightly inhibited by BAY u9773, the CysLT(1) and CysLT(2) receptor antagonist, in the human and guinea-pig oesophageal muscularis mucosae respectively. These indicate the existence of the CysLT(1) mediating oesophageal contraction in both human and guinea-pig oesophagus. The LTD4-induced contraction was not affected by tetrodotoxin, atropine or capsaicin, suggesting a direct effect. These results demonstrate that cysteinyl leucotrienes but not the dihydroxy leucotriene cause contraction in the human and guinea-pig oesophagus. CysLT(1) mediates contraction in both human and guinea-pig oesophagus.