A novel analog of TRH, YM14673, causes a decrease in brain TRH receptors in vitro

Biochemical mechanisms by which analogs of thyrotropin-releasing hormone (TRH) produce their potent neuropharmacological actions on the brain remain ill-defined. We tested effects of YM14673, a novel analog of TRH, on TRH receptors in rat brains in vitro. No significant binding of [3H]YM14673 to brain plasma membranes occurred. In contrast, preincubation of membranes with YM14673 caused dose-dependent decreases in TRH binding. This was not due to competition for TRH binding sites or existence of metabolites of YM14673. Preincubation with DN1417 (an another TRH analog), cyclo(His-Pro) or methionine-enkephalin did not affect the binding. Affections of YM14673 on TRH binding were observed when cerebral cortical membranes were studied; those were not seen in membranes prepared from hypothalamus, striatum, midbrain, hippocampus, or pons-medulla. The present data indicate that YM14673 exerts its characteristic neuro-pharmacological functions through interacting with TRH binding sites in the brain.