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Pranlukast prevents cysteinyl leukotriene‐induced emesis in the least shrew (Cryptotis parva)
Author(s) -
Chebolu Seetha,
Wang Yaozhi,
Ray Andrew,
Darmani Nissar A
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.969.10
Subject(s) - vomiting , leukotriene , leukotriene d4 , antagonist , leukotriene receptor , pharmacology , receptor , chemistry , receptor antagonist , medicine , asthma
Chemotherapeutic agents activate multiple signaling systems, including the cascade of arachidonic acid metabolites, of which some have emetic potential (e.g. PG F 2α ). The aims of this study were to test the emetic potential of one family of the neglected metabolites, the leukotrienes (LTA 4 , LTB 4 , LTF 4 , and the cysteinyl leukotrienes LTC 4 , LTD 4 and LTE 4 ), and to investigate whether the cysteinyl leukotriene CysLT 1 receptor antagonist pranlukast can prevent the LTC 4 induced emesis. Least shrews were injected with varying doses of one of the six tested leukotrienes and vomiting parameters were measured for 30 minutes. LTC 4 and LTD 4 were most efficacious, and significantly increased both the frequency and percentage of animals vomiting at doses from 0.1 and 0.05 mg/kg, respectively. The emetic profile of the cysteinyl leukotrienes (LTC 4 =LTD 4 >LTE 4 ) suggests CysLT 2 receptors have a key role in emesis whereas pranlukast which dose‐dependently, and at 10 mg/kg completely blocked LTC 4 ‐induced vomiting, implicates a leukotriene CysLT 1 receptor‐mediated emetic effect. Fos immunoreactivity, measured subsequent to LTC 4 ‐induced vomiting, was significantly increased in the enteric nervous system and medullary dorsal vagal complex following LTC 4 (P < 0.05) versus vehicle administration. This study is the first to show that some leukotrienes induce emesis, possibly involving both central and peripheral leukotriene CysLT 1 and/or leukotriene CysLT 2 receptors. This work was supported by NIH grant # R01CA115331 from the National Cancer Institute to Dr. Darmani.