The high-affinity Na+-Cl−–coupled membrane transporters play a crucial role in the reuptake of GABA and glycine from the presynaptic terminal and neighboring glia. These transporters, belonging to the solute carrier 6 (SLC6) family, are responsible for the uptake of these neurotransmitters as well as the biogenic amine neurotransmitters. However, they are distinct from the transporters for glutamate. To transport the neurotransmitter into the cell, two Na+ ions and one Cl− ion are co-transported. In the central nervous system (CNS), GAT1 and GAT3 are the highly expressed genes among the four GABA transporters identified (GAT1, GAT2, GAT3, and BGT1). The expression of these transporters may vary depending on the region and species, being found in neurons and/or glia. GlyT1 and GlyT2 are the two main glycine transporters. GlyT1 is predominantly found on astrocytes throughout the CNS, while GlyT2 is primarily located on glycinergic nerve terminals in the spinal cord, brainstem, and cerebellum.

The neurotransmitters dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin (5-hydroxytryptamine [5-HT]), and histamine, which also function as hormones outside the nervous system, are categorized as amines and act as neurotransmitters. Dopamine, norepinephrine, and epinephrine belong to the catecholamines group and share a common biosynthetic pathway originating from the amino acid tyrosine. Tyrosine hydroxylase converts tyrosine to L-dopa, and then dopa-decarboxylase converts L-dopa to dopamine. In dopaminergic neurons, the synthesis stops at dopamine, while in noradrenergic neurons, dopamine β-hydroxylase converts dopamine to norepinephrine. Epinephrine is produced by adding a methyl group to norepinephrine via phenylethanolamineN-methyl transferase. Serotonin is synthesized from tryptophan, an essential amino acid, in serotoninergic neurons. Tryptophan 5-hydroxylase converts tryptophan to 5-hydroxytryptophan, which is then further converted to serotonin by aromatic L-amino acid decarboxylase. Histamine, on the other hand, is synthesized from histidine in histaminergic neurons through the action of histidine decarboxylase.

Biogenic amines released at synapses are typically removed by reuptake into glia and neurons via Na+-Cl−–dependent transporters. The catecholamines are subsequently degraded by monoamine oxidase and catechol Omethyltransferase enzymes. Glutamate, an excitatory amino acid, is transported across the plasma membrane by at least five transporters (EAAT1 to EAAT5) belonging to the Na+-K+–dependent family. The transport of each glutamate molecule is driven by the co-transport of three Na+ ions and one H+ ion, as well as the countertransport of one K+ ion out of the cell.
After GABA and glycine are released from the presynaptic terminal, they are taken back up into the nerve terminal and neighboring glia by high-affinity Na+-Cl−–coupled membrane transporters. These Na+-Cl− transporters are part of what is called the solute carrier 6 (SLC6) family of transporters that also includes those for the biogenic amine neurotransmitters, but it is distinct from those for glutamate. Transport of the neurotransmitter into the cell is accomplished by symport with two Na+ and one Cl− ion. Four GABA transporter (GAT1, GAT2, GAT3, and BGT1) genes have been identified; however, GAT1 and GAT3 are the ones that are highly expressed in the CNS. Depending on region and species, they may be expressed in neurons and/or in glia. There are two main glycine transporters, GlyT1 and GlyT2. GlyT1 is found predominantly on astrocytes and is present throughout the CNS. In contrast, GlyT2 is located on glycinergic nerve terminals and is largely restricted to the spinal cord, brainstem, and cerebellum.
Many of the neurotransmitters in this category may be familiar because they have roles outside the nervous system, often as hormones. Among the amines known to act as neurotransmitters are dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), serotonin (5-hydroxytryptamine [5-HT]), and histamine. Dopamine, norepinephrine, and epinephrine are catecholamines, and they share a common biosynthetic pathway that starts with the amino acid tyrosine. Tyrosine is converted to L-dopa by the enzyme tyrosine hydroxylase. L-Dopa is then converted to dopamine by dopa-decarboxylase. In dopaminergic neurons, the pathway stops here. In noradrenergic neurons, another enzyme, dopamine β-hydroxylase, converts dopamine to norepinephrine. Epinephrine is obtained by adding a methyl group to norepinephrine via phenylethanolamineN-methyl transferase. In serotoninergic neurons, serotonin is synthesized from the essential amino acid tryptophan. Tryptophan is first converted to 5-hydroxytryptophan by tryptophan 5-hydroxylase, which is then converted to serotonin by aromatic L-amino acid decarboxylase. Finally, in histaminergic neurons the conversion of histidine to histamine is catalyzed by histidine decarboxylase.
Removal of synaptically released biogenic amines is generally accomplished by reuptake into glia and neurons via transporters belonging to the Na+-Cl−–dependent transporter family. The catecholamines are then degraded by two enzymes, monoamine oxidase and catechol Omethyltransferase.
Atleastfivetransporters(EAAT1toEAAT5,inwhichEAAT standsforexcitatory amino acid transporter)thatcarryglutamateacrosstheplasmamembranehavebeenidentified.TheyareallpartoftheNa+-K+–dependentfamilyoftransporters.InwardmovementofeachglutamatemoleculeisdrivenbythecotransportofthreeNa+ ionsandoneH+ ionandthecountertransportofoneK+ ionoutofthecell(see