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.