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Phe 13 , Tyr 19 ‐Melanin‐Concentrating Hormone and the Blood—Brain Barrier
Author(s) -
Kastin Abba J.,
Akerstrom Victoria,
Hackler Laszlo,
Zadina James E.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0740385.x
Subject(s) - blood–brain barrier , albumin , melanin concentrating hormone , chemistry , sodium dodecyl sulfate , capillary electrophoresis , endocrinology , serum albumin , medicine , hormone , gel electrophoresis , blood proteins , biochemistry , central nervous system , chromatography , biology , receptor , neuropeptide
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 bloodbrain 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 125 I‐Phe 13 , Tyr 19 ‐MCH did not cross faster than 99m Tc‐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 Phe 13 , Tyr 19 ‐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 Phe 13 , Tyr 19 ‐MCH added to blood migrated with a large‐molecular‐weight substance. Sodium dodecyl sulfate—capillary gel electrophoresis of Phe 13 , Tyr 19 ‐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 Phe 13 , Tyr 19 ‐MCH does not significantly cross the BBB, probably because of its binding to serum proteins.