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

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-...

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Veröffentlicht in:European journal of pharmacology 1989-05, Vol.164 (1), p.77-83
Hauptverfasser: Vonhof, Stefan, Paakkari, Ilari, Feuerstein, Giora, Cohen, Louis A., Labroo, Virender M.
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Sprache:eng
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Zusammenfassung: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 μM) 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 [ 3H][3Me-His 2]-TRH or through mechanisms not involving TRH receptors as such.
ISSN:0014-2999
1879-0712
DOI:10.1016/0014-2999(89)90233-1