Slow penetration of thyrotropin-releasing hormone across the blood-brain barrier of an in situ perfused guinea pig brain

J Neurochem. 1988 Jul;51(1):252-7. doi: 10.1111/j.1471-4159.1988.tb04864.x.


Transport of 3H-labelled thyrotropin-releasing hormone (TRH) across the blood-brain barrier was studied in the ipsilateral perfused in situ guinea pig forebrain. The unidirectional transfer constant (Kin) calculated from the multiple time brain uptake analysis ranged from 1.14 X 10(-3) to 1.22 X 10(-3) ml min-1 g-1, in the parietal cortex, caudate nucleus, and hippocampus. Regional Kin values for [3H]TRH were significantly reduced by 43-48% in the presence of an aminopeptidase and amidase inhibitor, 2 mM bacitracin, suggesting an enzymatic degradation of tripeptide during interaction with the blood-brain barrier. In the presence of unlabelled 1 mM TRH and 2 mM bacitracin together, a reduction of [3H]TRH regional Kin values similar to that obtained with 2 mM bacitracin alone was obtained . L-Prolinamide, the N-terminal residue of tripeptide, at a 10 mM level had no effect on the kinetics of entry of [3H]TRH into the brain. The data indicate an absence of a specific saturable transport mechanism for TRH presented to the luminal side of the blood-brain barrier. It is concluded that intact TRH molecule may slowly penetrate the blood-brain barrier, the rate of transfer being some three times higher than that of D-mannitol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacitracin / pharmacology
  • Blood-Brain Barrier*
  • Brain / blood supply
  • Brain / drug effects
  • Brain / metabolism*
  • Capillary Permeability
  • Female
  • Guinea Pigs
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Mannitol / metabolism
  • Parietal Lobe / drug effects
  • Parietal Lobe / metabolism
  • Perfusion
  • Proline / analogs & derivatives
  • Proline / pharmacology
  • Thyrotropin-Releasing Hormone / metabolism*


  • Bacitracin
  • Mannitol
  • Thyrotropin-Releasing Hormone
  • Proline
  • prolinamide