Norvaline2-TRH: binding to TRH receptors in rat brain homogenates

Eur J Pharmacol. 1990 May 3;180(1):1-12. doi: 10.1016/0014-2999(90)90586-u.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Stem / drug effects
  • Brain Stem / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Filtration
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • In Vitro Techniques
  • Kinetics
  • Male
  • Pyrrolidonecarboxylic Acid / analogs & derivatives
  • Rats
  • Rats, Inbred Strains
  • Receptors, Neurotransmitter / metabolism*
  • Receptors, Thyrotropin-Releasing Hormone
  • Thyrotropin-Releasing Hormone / analogs & derivatives*
  • Thyrotropin-Releasing Hormone / metabolism

Substances

  • Receptors, Neurotransmitter
  • Receptors, Thyrotropin-Releasing Hormone
  • thyrotropin-releasing hormone, 3-Me-
  • Thyrotropin-Releasing Hormone
  • thyrotropin-releasing hormone, nVal(2)-
  • Pyrrolidonecarboxylic Acid