Open AccessDiverging Effects of 5‐HT 3 Receptor Antagonists Ondansetron and Granisetron on Estramustine‐Inhibited Cellular Potassium Transport
Author(s) -
BehnamMotlagh Parviz,
Sandström PerErik,
Henriksson Roger,
Grankvist Kjell
Publication year - 2001
Publication title -
pharmacology & toxicology
Language(s) - English
Resource type - Journals
eISSN - 1600-0773
pISSN - 0901-9928
DOI - 10.1111/j.1600-0773.2001.880504.x
Subject(s) - granisetron , ondansetron , chemistry , pharmacology , 5 ht3 receptor , estramustine , antiemetic , serotonin , endocrinology , receptor , medicine , 5 ht receptor , biochemistry , chemotherapy , cancer , prostate disease , prostate cancer , nausea
We used 86 Rb + (K + analogue) to study potassium influx during the interaction of highly specific 5‐HT 3 ‐receptor antagonists, ondansetron and granisetron, with the effects of the anticancer drug, estramustine phosphate, on P31 mesothelioma cells. Estramustine phosphate (80 mg/l, 142 μmol/l) for 120 min. reduced 86 Rb + influx by 18.7%. The reduction was inhibited by ondansetron (0.1 μmol/l), but augmented by granisetron (0.1 μmol/l). Serotonin (1.0 μmol/l) antagonized ondansetron inhibition and restored granisetron‐augmented reduction of estramustine phosphate‐induced 86 Rb + influx to the level of the drug itself. Estramustine phosphate inhibited cellular Na + , K + , 2Cl − ‐cotransport activity whereas Na + , K + , ATPase activity was unaffected. Ondansetron blockade of estramustine phosphate‐induced reduction of 86 Rb + influx was due to increased Na + , K + , ATPase and Na + , K + , 2Cl − ‐cotransport whereas augmentation of estramustine phosphate‐induced reduction of 86 Rb + influx by granisetron, or combination of 5‐HT 3 receptor antagonists with serotonin was due mainly to inhibition of cellular Na + , K + , ATPase activity. Thus, ondansetron possesses a distinct ability to reverse K + influx of tumour cells exposed to estramustine phosphate whereas granisetron does not, due to different effect on cellular Na + , K + , ATPase and Na + , K + , 2Cl − ‐cotransport activity. Highly 5‐HT 3 receptor‐specific antiemetic agents may have different effects on ion transport of tumour cells during treatment with cytotoxic drugs.