Preprint Review Version 1 NOT YET PEER-REVIEWED

How Glutamate Is Managed by the Blood-Brain Barrier

  1. Department of Physiology & Biophysics, The Chicago MedicalSchool, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60088, USA
  2. Department of Biochemistry and Molecular Biology, Faculty of Medicine and Odontology, University of Valencia, Valencia 46010, Spain
Version 1 : Received: 22 September 2016 / Approved: 23 September 2016 / Online: 23 September 2016 (03:23:29 CEST)

A peer-reviewed article of this Preprint also exists.

Hawkins, R.A.; Viña, J.R. How Glutamate Is Managed by the Blood–Brain Barrier. Biology 2016, 5, 37. Hawkins, R.A.; Viña, J.R. How Glutamate Is Managed by the Blood–Brain Barrier. Biology 2016, 5, 37.

Journal reference: Biology 2016, 5, 37
DOI: 10.3390/biology5040037

Abstract

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

Subject Areas

glutamate; glutamine; BBB (blood brain-barrier); brain; oxoproline; amino acid transport

Readers' Comments and Ratings (0)

Discuss and rate this article
Views 92
Downloads 126
Comments 0
Metrics 0
Discuss and rate this article

×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.