Receptor binding of fluorinated histidine analogs of thyrotropin-releasing hormone in various regions of the rat brain.
Binding properties of [4(5)-fluoro-imidazole-His2]-TRH (4(5)-F-TRH), [2-trifluoromethyl-imidazole-His2]-TRH (2-CF3-TRH) and [4(5)-trifluoromethyl-imidazole-His2]-TRH (4(5)-CF3-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 (Ki = 7.5-13.5 microM). 2-CF3-TRH, an analog of less cardiovascular but increased prolactin-releasing activity, shows Ki values of 3.3-4.9 microM. 4(5)-CF3-TRH, which shows comparable biological activity to 2-CF3-TRH, demonstrates a binding affinity which is virtually nonspecific (Ki = 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-His2]-TRH or through mechanisms not involving TRH receptors as such.
Vonhof
S
S
Laboratory of Chemistry, National Institutes of Health, Bethesda, MD 20892.
Paakkari
I
I
Feuerstein
G
G
Cohen
L A
LA
Labroo
V M
VM
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006639:Histidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D011988:Receptors, Thyroid Hormone; D006639:Histidine