Norvaline super(2)-TRH: Binding to TRH receptors in rat brain homogenates

Norvaline super(2)-thyrotropin-releasing hormone ((Nva super(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. The authors evaluated the receptor-binding properties of (Nva super(2))TRH in homogenates of rat anterior pituitary, hypothalamus, brainstem and cortex tissue, using ( super(3)H)TRH and ( super(3)H)(3-Me-His super(2))TRH as radioligands. Additionally, (Nva super(2))TRH was shown to compete with ( super(3)H)TRH at low affinity TRH-binding sites with similar affinities. It is concluded that the loss of TSH-releasing activity of (Nva super(2))TRH appears to be due to a drastic reduction in binding affinity to the high affinity TRH receptor subtype.