Properties and distribution of TRH receptors in normal and spastic mutant mouse brain and spinal cord

Specific binding sites for thyrotropin-releasing hormone (TRH) were labelled with the potent analog, [(3)H] (3-Me-His(2))TRH, in the brain and spinal cord of the mutant mouse spastic and nonafflicted littermate controls. Equilibrium binding parameters determined from competition assays indicated dissociation constant (K(d)) of 4-5 nM in selected regions of the brain in both groups of animals. Detailed examination of the TRH receptor density at 1 nM [(3)]MeTRH concentration revealed a marked heterogeneous distribution (amygdala hippocampus = n. accumbens/striatum ? midbrain > spinal cord > pons/medulla = hypothalamus ? cerebellum) . An almost identical anatomical localization profile of TRH receptors was apparent in control and spastic mice. The pharmacological specificity of [(3)H]MeTRH binding sites in the spinal cord and amygdala of these animals was again closely similar and resembled that documented previously for other mammalian species. In conclusion, TRH receptors in spastic mutant mice exhibit similar properties and brain regional distribution as their normal counterparts.