Description
Metabotropic glutamate receptors (mGluR1-
8) are G protein-
coupled receptors that function to modulate brain excitatory signaling
via presynaptic, postsynaptic, and glial mechanisms. DL-
AP3 is a competitive mGluR1 antagonist that demonstrates a K
i value of 298 μM and an IC
50 value of 1mM for rat mGluR1α when challenged with glutamate. DL-
AP3 can antagonize excitatory amino acid-
induced phosphoinositide hydrolysis, induce Ca
2+ mobilization in rat hippocampal slices, and inhibit phosphoserine phosphatase in rat brain cortex. At concentrations from 10-
300 μM DL-
AP3 has been used to characterize the role of mGluR in long-
term potentiation in the hippocampus in a model of learning and memory, the release of glutamate in Parkinson’s disease, and the increased activity of mGluR implicated in fragile X syndrome.
Uses
DL-2-Amino-3-phosphonopropionic acid (AP3) is an inhibitor of phosphoserine phosphatase and mGluR. Also known as the antagonist of a receptor that is coupled to phosphoinositide metabolism in brain slices. D,L-2-Amino-3-phosphonopropionic acid is also an inhibitor of metabotropic glutamate receptors in rat brain.
Definition
ChEBI: 2-amino-3-phosphonopropanoic acid is a non-proteinogenc alpha-amino acid that is alanine in which one of the hydrogens of the terminal methyl group has been replaced by a dihydroxy(oxido)-lambda(5)-phosphanyl group. It has a role as a metabotropic glutamate receptor antagonist and a human metabolite. It is a non-proteinogenic alpha-amino acid, a member of phosphonic acids and an alanine derivative.
in vivo
DL-AP3 (4mg/kg, i.p., for 5weeks) with SKF81297 (1mg/kg, i.p.) reduces the hyperactivity phenotype in Fmr1 KO mice[3].
DL-AP3 (4.0-12.0 mg/animal, i.c.v. infusion, 100 μL) blocks development of visceral pain symptoms and neuroendocrinological changes in the blood plasma of sheep[4].
| Animal Model: | Fmr1 KO mice[3] |
| Dosage: | 4mg/kg with SKF81297 (1mg/kg) |
| Administration: | i.p., for 5weeks. |
| Result: | Reduced the distance traveled by Fmr1 KO mice (open-field test).
Reduced the swim latency on the final day in the Fmr1 KO mice (Morris Water Maze test).
|
| Animal Model: | Sheep with visceral pain evoked by colonic distension (CD)[4] |
| Dosage: | 4.0-12.0 mg/animal |
| Administration: | i.c.v. infusion, 100 μL |
| Result: | Decreased intensity from appearance of clinical signs of visceral pain caused by CD test.
Diminished the increase of plasma cortisol, E, NE and DA concentrations caused by visceral pain provoked by CD episode.
|
References
[1] DARRYLE D. SCHOEPP James A M David E Jane. Pharmacological agents acting at subtypes of metabotropic glutamate receptors[J]. Neuropharmacology, 1999, 38 10: Pages 1431-1476. DOI:
10.1016/s0028-3908(99)00092-1[2] JON E. HAWKINSON Paul L W Manuel Acosta Burruel. The metabotropic glutamate receptor antagonist l-2-amino-3-phosphonopropionic acid inhibits phosphoserine phosphatase[J]. European journal of pharmacology, 1996, 307 2: Pages 219-225. DOI:
10.1016/0014-2999(96)00253-1[3] S OTANI W B L J A Connor. Long-term potentiation and evidence for novel synaptic association in CA1 stratum oriens of rat hippocampus.[J]. Learning & memory, 1995, 2 2: 101-106. DOI:
10.1101/lm.2.2.101[4] HAO LI Gang H Jian Hua Ding. Group I mGluR ligands fail to affect 6-hydroxydopamine- induced death and glutamate release of PC12 cells.[J]. Acta Pharmacologica Sinica, 2003, 24 7: 641-645.
[5] ZHAO-HUI XU. Group I mGluR antagonist rescues the deficit of D1-induced LTP in a mouse model of fragile X syndrome.[J]. Molecular Neurodegeneration, 2012, 7: 24. DOI:
10.1186/1750-1326-7-24
