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Modulation of Receptors for Thyrotropin‐Releasing Hormone by Benzodiazepines: Brain Regional Differences
Author(s) -
Sharif Najam A.,
Burt David R.
Publication year - 1984
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1984.tb12795.x
Subject(s) - thyrotropin releasing hormone , receptor , chemistry , medicine , endocrinology , flurazepam , chlordiazepoxide , hypothalamus , pharmacology , hormone , diazepam , benzodiazepine , biochemistry , biology
The benzodiazepines (BZDs) chlordiazepoxide (CDE), diazepam (DZM), and flurazepam (FLM) inhibited receptor binding for thyrotropin‐releasing hormone (TRH) with low micromolar potency. In contrast, numerous other categories of drugs were previously shown to be inactive. Scatchard analysis of competition data suggested that the BZDs reduced TRH receptor affinity, consistent with competitive inhibition. Receptors from amygdala, retina, and pituitary appeared more sensitive to inhibition by BZDs than those from hypothalamus, hippocampus, spinal cord, or cerebellum. The latter four regions also gave shallower inhibition curves. CDE revealed an apparently biphasic dissociation of [ 3 H][3‐Me‐His 2 ]TRH([ 3 H]MeTRH) from amygdala membranes at 4°C, with kinetics similar to those with TRH. These results suggest that TRH receptors in the brain are heterogeneous and that certain BZDs in high therapeutic concentrations may exert central effects through actions at TRH receptors or coupled proteins.