Receptor binding of fluorinated histidine analogs of thyrotropin-releasing hormone in various regions of the rat brain

Abstract Binding properties of [4(5)-fluoro-imidazole-His 2 ]-TRH (4(5)-F-TRH), [2-trifluoromethyl-imidazole-His 2 ]-TRH (2-CF 3 -TRH) and [4(5)-trifluoromethyl-imidazole-His 2 ]-TRH (4(5)-CF 3 -TRH), three novel TRH analogs, have been evaluated in rat pituitary, hypothalamus, brainstem and cortex tissue. 4(5)-F-TRH, previously shown to elicit arterial pressor responses and prolactin release similar to those of TRH, binds to TRH receptors with low, micromolar affinity (K i = 7.5−13.5 μ M) 2-CF 3 -TRH, an analog of less cardiovascular but increased prolactin-releasing activity, shows K i values of 3.3–4.9 μM. 4(5)-CF 3 -TRH, which shows comparable biological activity to 2-CF 3 -TRH, demonstrates a binding affinity which is virtually nonspecific (K i = 0.39−1.01 mM). It is therefore concluded that the biological effects of these analogs are mediated either through low affinity TRH binding sites not recognized by [ 3 H][3Me-His 2 ]-TRH or through mechanisms not involving TRH receptors as such.