Identification of Gly-Pro-Glu (GPE), the aminoterminal tripeptide of insulin-like growth factor 1 which is truncated in brain, as a novel neuroactive peptide.
A truncated form of IGF-1 which lacks the aminoterminal tripeptide Gly-Pro-Glu (GPE) is found in human brain. It was proposed that GPE may result from neural specific processing and also have a function within the CNS. GPE was synthesized and shown to inhibit glutamate binding to the N-methyl-D-aspartate (NMDA) receptor. Whilst the carboxyterminal glutamate was necessary for NMDA receptor binding, the aminoterminal glycine potentiated receptor crossreaction. Furthermore, GPE had a potent stimulatory effect on the potassium induced release of acetylcholine from rat cortical slices. A less potent stimulation of dopamine release from striatum was also observed. The specific competitive NMDA receptor antagonist, (+/-)2-amino-7-phosphonoheptanoate (AP7), inhibited the action of GPE on dopamine but not on acetylcholine release. These studies have identified GPE as a novel neuroactive peptide with a potent action on acetylcholine release and support the general concept that the proteolytic products of the IGF-1 precursor play a role in the regulation of brain function.
Sara
V R
VR
Karolinska Institute's Department of Pathology, Karolinska Hospital, Stockholm, Sweden.
Carlsson-Skwirut
C
C
Bergman
T
T
Jörnvall
H
H
Roberts
P J
PJ
Crawford
M
M
Håkansson
L N
LN
Civalero
I
I
Nordberg
A
A
D000109:Acetylcholine / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007700:Kinetics; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000302:isolation & purification*; D009842:Oligopeptides / Q000138:chemical synthesis / Q000302:isolation & purification* / Q000494:pharmacology; D010296:Parietal Lobe / Q000187:drug effects / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000235:genetics*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D005971:Glutamates; D009479:Neuropeptides; D009842:Oligopeptides; D011956:Receptors, Cell Surface; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017451:Receptors, Somatomedin; D013002:Somatomedins; D018698:Glutamic Acid; D007334:Insulin-Like Growth Factor I; D000109:Acetylcholine; D004298:Dopamine; C062053:glycyl-prolyl-glutamic acid