Phe(13),Tyr(19)-melanin-concentration hormone and the blood-brain barrier: role of protein binding.
J Neurochem
; 74(1): 385-91, 2000 Jan.
Article
em En
| MEDLINE
| ID: mdl-10617143
Melanin-concentrating hormone (MCH), found both peripherally and centrally, is involved in food ingestion. Although its expression in brain is increased by fasting, it is not known whether it crosses the blood-brain barrier (BBB). Use of the sensitive method of multiple-time regression analysis has shown that almost all of the peptides and polypeptides tested cross the BBB at a rate faster than the vascular marker albumin. With this same method, however, we found that the 19-amino acid 125I-Phe13,Tyr19-MCH did not cross faster than 99mTc-albumin. Several mechanisms were excluded as possible explanations for the slow rate of influx. These included degradation, association with capillary endothelial cells, and transport from brain to blood. When Phe13,Tyr19-MCH was perfused in blood-free buffer, however, it entered the brain significantly faster than albumin. This suggested protein binding as an explanation for the slow rate of influx when the MCH was administered in blood. Protein binding was confirmed by capillary zone electrophoresis, which showed that almost all of the Phe13,Tyr19-MCH added to blood migrated with a large-molecular-weight substance. Sodium dodecyl sulfate-capillary gel electrophoresis of Phe13,Tyr19-MCH in buffer additionally showed that the MCH aggregated as a trimer, a factor not preventing its influx by blood-free perfusion. Thus, the results show that blood-borne Phe13,Tyr19-MCH does not significantly cross the BBB, probably because of its binding to serum proteins.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hormônios Hipofisários
/
Barreira Hematoencefálica
/
Hormônios Hipotalâmicos
/
Melaninas
Limite:
Animals
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos
País de publicação:
Reino Unido