Modulation of receptors for thyrotropin-releasing hormone by benzodiazepines: brain regional differences.

Abstract:

: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-Me-His2]TRH([3H]MeTRH) from amygdala membranes at 4 degrees 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.

journal_name

J Neurochem

authors

Sharif NA,Burt DR

doi

10.1111/j.1471-4159.1984.tb12795.x

subject

Has Abstract

pub_date

1984-09-01 00:00:00

pages

742-6

issue

3

eissn

0022-3042

issn

1471-4159

journal_volume

43

pub_type

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