Chlordiazepoxide is a competitive thyrotropin-releasing hormone receptor antagonist in GH3 pituitary tumour cells.
Addition of thyrotropin-releasing hormone (TRH) to [3H]-inositol pre-labelled GH3 pituitary tumour cells suspended in medium containing 10mM lithium chloride led to a rapid diminution in cellular [3H]-inositol and increase in [3H]-inositol 1-phosphate (InslP), [3H]-inositol bisphosphate (InsP2) and [3H]-inositol trisphosphate (InsP3). In the presence of the benzodiazepine tranquillizer, chlordiazepoxide, the TRH concentration-response curves for these effects were shifted to the right in a parallel fashion. The Ki for chlordiazepoxide in inhibiting all four responses was 1.5 X 10(-5)M. Chlordiazepoxide did not inhibit the small bombesin-induced rise in [3H]-InslP. Another benzodiazepine, diazepam, was less active. The TRH-induced rise in cytosolic free calcium monitored in Quin-2-loaded GH3 cells was also blocked by chlordiazepoxide in a competitive manner, while that induced by high K+-induced depolarisation was unaffected. It is suggested that chlordiazepoxide acts as a competitive antagonist at the level of the TRH receptor.
Drummond
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D000818:Animals; D001839:Bombesin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002707:Chlordiazepoxide / Q000494:pharmacology*; D003975:Diazepam / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism
D007295:Inositol Phosphates; D011956:Receptors, Cell Surface; D018025:Receptors, Thyrotropin-Releasing Hormone; D007294:Inositol; D013973:Thyrotropin-Releasing Hormone; D002707:Chlordiazepoxide; D001839:Bombesin; D003975:Diazepam; D002118:Calcium