Binding sites for thyrotropin-releasing hormone in sheep nucleus accumbens resemble pituitary receptors

TRH binds to sites in the nucleus accumbens-septal area of sheep brain. These sites appear to represent receptors for at least some of its behavioral effects in other species and are very similar to sheep pituitary receptors. All measurements were performed on ice to prevent peptide degradation. High affinity [3H]TRH binding in brain regions was distinguished from interfering low affinity binding by use of [3-Me-His2]TRH, a more potent and specific analog, in blank tubes at a 1-microM concentration. The nucleus accumbens-septal area, particularly the nucleus accumbens itself, showed the highest binding of any of a variety of brain regions surveyed. Binding sites in both nucleus accumbens and anterior pituitary had an equilibrium dissociation constant of about 20-40 nM, a rate constant for association of about 1-3 x 10(6) M-1 min-1, and a rate constant for dissociation of about 0.07 min-1. Seventeen TRH analogs showed closely similar potencies in competing for binding in the two tissues. Six weak analogs appeared to be more potent in the nucleus accumbens than in the pituitary, but this was an artifact of their relatively greater potency in competing for low affinity binding sites which are absent in pituitary. The only major difference between the high affinity binding sites in the two tissues was in their concentration, which was about 2- to 3-fold higher in the pituitary.