Excitatory amino acid neurotransmission. Pathways for metabolism, storage and reuptake of glutamate in brain.

Abstract

In the nervous system, glutamate is an excitatory aminoacid which at higher concentrations has been implicated in a number of disorders. Glutamate is stored in presynaptic vesicles and is released by calcium-dependent exocytosis. After its action on ionotropic receptors (iGluR, related to ionic channels) or metabotropic receptors (mGluR, related to metabolic formation of second messengers), glutamate can be removed from the synaptic cleft through two processes: re-uptake back into pre-synaptic terminals or diffusion out of synaptic cleft for uptake by glial cells. This is achieved by glutamate transporters. In pre-synaptic terminals, glutamate is packed into the specialized secretory vesicles by means of a specific vesicular transporter. The level of glutamate available for neurosecretion is regulated by the vesicular transport activity. In order to achieve a proper concentration of the neurotransmitter in synaptic vesicles, glutamate must be synthesized. Glutamine is obtained in astroglial cells from the glutamate reuptaken, and as it has no neurotransmitter activity, it is the metabolite which regenerates glutamate in neurones (glutamate-glutamine cycle). Moreover, glutamate is also obtained from glucose by an intermediate of TCA cycle. In this paper we want to introduce some aspects of glutamate biosynthesis and release: glutamate receptors, neurotransmitter uptake by the glutamate transporters and neurotransmitter inactivation and new formation by metabolism.