Pyroglutamate stimulates Na+ -dependent glutamate transport across the blood-brain barrier.
Regulation of Na(+)-dependent glutamate transport was studied in isolated luminal and abluminal plasma membranes derived from the bovine blood-brain barrier. Abluminal membranes have Na(+)-dependent glutamate transporters while luminal membranes have facilitative transporters. This organization allows glutamate to be actively removed from brain. gamma-Glutamyl transpeptidase, the first enzyme of the gamma-glutamyl cycle (GGC), is on the luminal membrane. Pyroglutamate (oxoproline), an intracellular product of GGC, stimulated Na(+)-dependent transport of glutamate by 46%, whereas facilitative glutamate uptake in luminal membranes was inhibited. This relationship between GGC and glutamate transporters may be part of a regulatory mechanism that accelerates glutamate removal from brain.
Hawkins
Richard A
RA
Department of Physiology and Biophysics, The Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064-3095, USA. rah@post.harvard.edu
Simpson
Ian A
IA
Mokashi
Ashwini
A
Viña
Juan R
JR
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*
D018698:Glutamic Acid; D012964:Sodium; D011761:Pyrrolidonecarboxylic Acid