Cysteinyl Leukotriene Receptor Type 1 (CysLT 1) Mediates Contraction of the Guinea Pig Lower Esophageal Sphincter

Abstract

Objective Leukotriene D 4 (LTD 4) causes contraction of the cat lower esophageal sphincter. The effects of leukotrienes in the guinea pig lower esophageal sphincter and the cysteinyl leukotriene receptor (CysLT) subtype that mediate this contraction are not known. The purpose of the present study was to characterize the CysLT receptors in the guinea pig lower esophageal sphincter. Materials and Methods We measured the contractions of transverse strips from the guinea pig lower esophageal sphincter caused by cysteinyl leukotrienes, LTC 4, LTD 4 and LTE 4, and the dihydroxy leukotriene, LTB 4. We also measured LTD 4-induced contraction inhibited by CysLT receptor antagonists, tetrodotoxin and atropine. Results In the guinea pig lower esophageal sphincter strips, LTC 4, LTD 4 and LTE 4, but not LTB 4, caused concentration-dependent contractions. The relative potencies for cysteinyl leukotrienes to cause contraction were LTD 4 = LTC 4 > LTE 4. LTE 4 was a partial agonist. The LTD 4-induced contraction was inhibited by two selective CysLT 1 receptor antagonists, montelukast and zafirlukast, and by the dual CysLT 1 and CysLT 2 receptor antagonist BAY u9773. The combination of both montelukast and BAY u9773 did not potentiate the inhibition caused by montelukast alone. These findings indicate that CysLT 1 mediates the contraction in the lower esophageal sphincter. Furthermore, LTD 4-induced contraction was not affected by tetrodotoxin or atropine, suggesting a direct effect. Conclusion These results demonstrate that cysteinyl leukotrienes, but not the dihydroxy leukotriene LTB 4, cause contraction of the guinea pig lower esophageal sphincter. The CysLT 1 receptor mediates this contraction.