Abstract
Properties of TRH-receptors in the rat central nervous system (CNS) were studied. MK-771 (L-gyro-2-aminoadipyl-histidyl-thiazolidine-4-car-boxamide) and DN-1417 (γ-butyrolactone-γ-carbonyl-histidyl-prolinamide citrate), potent TRH analogs, had relative potencies of 170% and 30%, respectively, of TRH in the radioreceptor assay. Most of the other TRH analogs which were tested had little potency in reducing the receptor binding of [3H]TRH, indicating that the tertiary structure of the TRH molecule is necessary for binding to the brain receptor. The receptor activity was sensitive to digestion by trypsin or phospholipase A, suggesting that protein and phospholipid moieties are essential for the binding of [3H]TRH. Thiol reagents reduced the binding activity of the receptor, suggesting that an intrcahain disulfide bond may be an important constituent of the binding site for TRH. A therapeutic serum level of Li+ (1 mM) decreased the binding of [3H]TRH, and physiological serum concentrations (20μM) of Cu2+, Zn2+ and Pe2+ increased TRH binding. This indicates that the metal ions had primary significance in the function of CNS TRH-receptors.
