Cysteinyl Leukotriene Receptor Type 1 (CysLT₁) Mediates Contraction of the Guinea Pig Lower Esophageal Sphincter

Abstract 

Objective

Leukotriene D₄ (LTD₄) 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, LTC₄, LTD₄ and LTE₄, and the dihydroxy leukotriene, LTB₄. We also measured LTD₄-induced contraction inhibited by CysLT receptor antagonists, tetrodotoxin and atropine.

Results

In the guinea pig lower esophageal sphincter strips, LTC₄, LTD₄ and LTE₄, but not LTB₄, caused concentration-dependent contractions. The relative potencies for cysteinyl leukotrienes to cause contraction were LTD₄ = LTC₄ > LTE₄. LTE₄ was a partial agonist. The LTD₄-induced contraction was inhibited by two selective CysLT₁ receptor antagonists, montelukast and zafirlukast, and by the dual CysLT₁ and CysLT₂ 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 CysLT₁ mediates the contraction in the lower esophageal sphincter. Furthermore, LTD₄-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 LTB₄, cause contraction of the guinea pig lower esophageal sphincter. The CysLT₁ receptor mediates this contraction.

Keywords:  Esophagus , Leukotriene , Leukotriene receptor antagonist , Motility

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