Norvaline2-TRH: binding to TRH receptors in rat brain homogenates.
Norvaline2-thyrotropin-releasing hormone ([Nva2]TRH) has been described as a thyrotropin-releasing hormone (TRH) analog with no thyrotropin (TSH)-releasing capacity but enhanced analeptic activity compared with TRH, as shown by the reversal of haloperidol-induced catalepsy. We have evaluated the receptor-binding properties of [Nva2]TRH in homogenates of rat anterior pituitary, hypothalamus, brainstem and cortex tissue, using [3H]TRH and [3H][3-Me-His2]TRH as radioligands. Apparent Ki values at high affinity TRH-binding sites, labelled predominantly by [3H][3-Me-His2]TRH, ranged from 17.0 to 36.9 microM in all tested regions. Additionally, [Nva2]TRH was shown to compete with [3H]TRH at low affinity TRH-binding sites with similar affinities. It is concluded that the loss of TSH-releasing activity of [Nva2]TRH appears to be due to a drastic reduction in binding affinity to the high affinity TRH receptor subtype. Its analeptic activity, however, may be mediated by low affinity TRH binding sites which are predominantly labelled by [3H]TRH or by yet unidentified mechanisms.
Vonhof
S
S
Laboratory of Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892.
Feuerstein
G Z
GZ
Cohen
L A
LA
Labroo
V M
VM
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005374:Filtration; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000378:metabolism
D017981:Receptors, Neurotransmitter; D018025:Receptors, Thyrotropin-Releasing Hormone; C014109:thyrotropin-releasing hormone, 3-Me-; D013973:Thyrotropin-Releasing Hormone; C047944:thyrotropin-releasing hormone, nVal(2)-; D011761:Pyrrolidonecarboxylic Acid