Slow Penetration of Thyrotropin‐Releasing Hormone Across the Blood‐Brain Barrier of an In Situ Perfused Guinea Pig Brain

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 × 10‐−3 to 1.22 × 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.