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 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.
D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D001812:Blood-Brain Barrier; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D002199:Capillary Permeability; D005260:Female; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008353:Mannitol / Q000378:metabolism; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D010477:Perfusion; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D001414:Bacitracin; D008353:Mannitol; D013973:Thyrotropin-Releasing Hormone; D011392:Proline; C056291:prolinamide