Department of Internal Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan
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.
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.
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.
Esophagus; Leukotriene; Leukotriene receptor antagonist; Motility