AP5 (also known as APV, (2''R'')-amino-5-phosphonovaleric acid, or (2''R'')-amino-5-phosphonopentanoate) is a chemical compound used as a biochemical tool to study various cellular processes. It is a selective

NMDA receptor antagonist NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the ''N''-Methyl-D-aspartate receptor ( NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce ...

that competitively inhibits the ligand (glutamate) binding site of

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...

s. AP5 blocks NMDA receptors in micromolar concentrations (~50 μM). AP5 blocks the cellular analog of

classical conditioning Classical conditioning (also known as Pavlovian or respondent conditioning) is a behavioral procedure in which a biologically potent stimulus (e.g. food) is paired with a previously neutral stimulus (e.g. a triangle). It also refers to the lear ...

in the sea slug ''

Aplysia californica The California sea hare (''Aplysia californica'') is a species of sea slug in the sea hare family, Aplysiidae.Rosenberg, G.; Bouchet, P. (2011). Aplysia californica J. G. Cooper, 1863. Accessed through: World Register of Marine Species at http:/ ...

'', and has similar effects on ''Aplysia''

long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...

(LTP), since NMDA receptors are required for both. It is sometimes used in conjunction with the

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar ...

chelator

BAPTA BAPTA (1,2-bis(''o''- amino phenoxy)ethane-''N'',''N'',''N′'',''N′''-tetra acetic acid) is a calcium-specific aminopolycarboxylic acid. The presence of four carboxylic acid functional groups makes possible the binding of two calcium ions. The e ...

to determine whether NMDARs are required for a particular cellular process. AP5/APV has also been used to study NMDAR-dependent LTP in the mammalian hippocampus.Gustafsson B., Wigström H., Abraham W.C., and Huang Y.Y. Long-Term Potentiation in the Hippocampus Using Depolarizing Current Pulses as the Conditioning Stimulus to Single Volley Synaptic Potentials. ''Journal of Neuroscience.'' 1987 March;7(3):774-780 In general, AP5 is very fast-acting within ''

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology a ...

'' preparations, and can block NMDA receptor action at a reasonably small concentration. The active

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Is ...

of AP5 is considered to be the D configuration, although many preparations are available as a

racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

mixture of D- and L-isomers. It is useful to isolate the action of other

glutamate Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...

receptors in the brain, i.e.,

AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, better known as AMPA, is a compound that is a specific agonist for the AMPA receptor, where it mimics the effects of the neurotransmitter glutamate. There are several types of glutamatergic ...

and

kainate receptor Kainate receptors, or kainic acid receptors (KARs), are ionotropic receptors that respond to the neurotransmitter glutamate. They were first identified as a distinct receptor type through their selective activation by the agonist kainate, a dru ...

s. AP5 can block the conversion of a

silent synapse In neuroscience, a silent synapse is an excitatory glutamatergic synapse whose postsynaptic membrane contains NMDA-type glutamate receptors but no AMPA-type glutamate receptors. These synapses are named "silent" because normal AMPA receptor-medi ...

to an active one, since this conversion is NMDA receptor-dependent.

References

External links

* Laube, B; Hirai H, Sturgess M, Betz H, and Kuhse J (1997). "Molecular determinants of antagonists discrimination by NMDA receptor subunits: Analysis of the glutamate binding site on the NR2B subunit". Neuron 18 (3): 493–503. . . {{Ionotropic glutamate receptor modulators NMDA receptor antagonists Amino acids Phosphonic acids

See also

References

External links