Abstract
Norvaline 2-thyrotropin-releasing hormone ([Nva 2]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 [Nva 2]TRH in homogenates of rat anterior pituitary, hypothalamus, brainstem and cortex tissue, using [ 3H]TRH and [ 3H][3-Me-His 2]TRH as radioligands. Apparent K i values at high affinity TRH-binding sites, labelled predominantly by [ 3H][3-Me-His 2]TRH, ranged from 17.0 to 36.9 μM in all tested regions. Additionally, [Nva 2]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 [Nva 2]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.
Published Version
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