Glutamic acid receptors
Glutamic acid present in presynaptic neuronal terminations is released into the synaptic cleft. It activates postsynaptic specific receptors, diffuses, is reuptaken by presynaptic terminations. Glutamate receptors can be divided into two groups, ionotropic receptors or and metabotropic receptors.
Ionotropic receptors
Ionotropic receptors induce a depolarization by opening channels permeable to Na+ and Ca 2+ ions which penetrate inside the cell. Opening of these channels could also allow potassium exit. They are subdivided in two types.
NMDA receptors
NMDA receptors, thus called because they are activated by N-methyl-D-aspartate, a very powerful agonis tare receptor-channels which opens when activated by glutamate and Na+ and especially Ca2+ ions enter into cells. NMDA receptor response is slower than that of non-NMDA receptors.
The activity of this receptor channel is modulated in an allosteric way by various compounds:
- glycine is essential to the activation of NMDA receptor by glutamate and to opening of the channel.
D-serine, synthesized by glial tissue from L-serine under influence of a racemase, also activates the glycine receptor of the NMDA complex making it receptive to glutamate. Antagonists of racemase could reduce D-serine formation and activity of receptor NMDA and to have an interest in treatment of strokes.
Cycloserine, which was used in the treatment of tuberculosis, could have a glycine-like effect. In animals it can facilitate memorizing.
Antagonists of glycine/NMDA receptor, such as derivatives of kynurenic acid, could have anticonvulsive properties.
- Some induce opening:
- polyamines like spermine
- molecules with HS group.
- Others inhibit opening:
- magnesium, whose inhibiting effect is voltage-dependant, blocks the channel while being inside the channel
- zinc which could act like magnesium
- tricyclic antidepressants
- protons.
Non-NMDA receptors
They are activated by compounds not used as drugs, quisqualate , kaïnate or propionic amino-hydroxy-methyl isoxazole acid (AMPA), and induce sodium entry into cells, but they are not very permeable to divalent cations. These receptors induce an early depolarization.
Metabotropic receptors
Metabotropic receptors, called mGlu1, mGlu2,.. mGlu8 act via G proteins and induce according to their type, stimulation of phospholipase C, inhibition of adenylcyclase, activation of A2 phospholipase, inhibition of opening of potassium channels or stimulation of phosphodiesterases as well as other complex effects, of which modulation of certain channels receptor-dependant. Metabotropic receptors could give noxious impulses at the thalamic level.
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