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The interaction of benzodiazepines with thyrotropin‐releasing hormone receptors on clonal pituitary cells
Author(s) -
Joels Lesley A.,
Drummond Alan H.
Publication year - 1989
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1989.tb11837.x
Subject(s) - thyrotropin releasing hormone , phosphatidylinositol , chemistry , receptor , bombesin , inositol phosphate , medicine , endocrinology , inositol , chlordiazepoxide , pharmacology , biochemistry , hormone , biology , signal transduction , neuropeptide , diazepam
1 Seven benzodiazepines were investigated for their ability to interact with receptors for thyrotropin‐releasing hormone (TRH) on GH 3 and GH 4 C 1 pituitary tumour cells. 2 Midazolam and chlordiazepoxide were the most potent inhibitors of TRH‐induced [ 3 H]‐inositol phosphate formation with K i values in the low micromolar range. The antagonism was competitive in nature and was increased in potency at sub‐physiological temperatures. 3 None of the agents examined antagonized bombesin‐induced [ 3 H]‐inositol phosphate formation in GH 4 C 1 cells. 4 While the ability of benzodiazepines to interact with the GABA receptor‐chloride channel ionophore is markedly stereospecific, little difference was evident in the ability of (+)− and (−)−4‐methylmidazolam (Ro 21–5656 and Ro 21–5657) to compete with TRH at its receptor. 5 Recently it has been suggested that, in contrast to phosphatidylinositol hydrolysis, the TRH‐induced breakdown of phosphatidylinositol polyphosphates is transient in clonal pituitary cells. Addition of chlordiazepoxide to TRH‐stimulated GH 3 cells up to 60 min after initiating the reaction leads, however, to an immediate decline in the cellular content of inositol trisphosphate. This indicates that TRH‐induced phosphatidylinositol 4,5‐bisphosphate hydrolysis is not transient.