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Monoamine Transporter
The monoamine neurotransmitter transporters (MATs) are part of the solute carrier 6 (SLC6) family of transporters. They are expressed in the central nervous system (CNS) among other places, where they play a critical al role in regulating monoamine neurotransmitter homeostasis. There are three types of MATs, namely dopamine transporter (DAT, SLC6A3), norepinephrine transporter (NET, SLC6A2), and serotonin transporter (SERT, SLC6A4) which mediate the uptake of monoamine neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT), respectively, from the extracellular space into the intracellular compartment. All three transporters are membrane-embedded proteins and in the CNS exclusively expressed in the presynaptic neuronal terminals of their respective pathways.
The MATs play a pivotal role in controlling the signal amplitude and duration of monoaminergic neurotransmission by altering the concentration of monoamines in the extracellular space of the CNS. MATs also undergo regulation directly or indirectly by a number of kinases e.g., protein kinase C (PKC), cAMP-dependent protein kinase (protein kinase A, PKA), cGMP-dependent protein kinase (protein kinase G), Ca2+/calmodulin-dependent protein kinase II, ERK1/2, p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt and tyrosine kinases. Careful design and interpretation of biochemical and behavioral assays to evaluate the function and pharmacology of MAT ligands is necessary to delineate them as competitive inhibitors, allosteric modulators, substrates or releasers.
References
1.Aggarwal S, Mortensen OV. Curr Protoc Pharmacol. 2017;79:12.16.1–12.16.17.
The MATs play a pivotal role in controlling the signal amplitude and duration of monoaminergic neurotransmission by altering the concentration of monoamines in the extracellular space of the CNS. MATs also undergo regulation directly or indirectly by a number of kinases e.g., protein kinase C (PKC), cAMP-dependent protein kinase (protein kinase A, PKA), cGMP-dependent protein kinase (protein kinase G), Ca2+/calmodulin-dependent protein kinase II, ERK1/2, p38 mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt and tyrosine kinases. Careful design and interpretation of biochemical and behavioral assays to evaluate the function and pharmacology of MAT ligands is necessary to delineate them as competitive inhibitors, allosteric modulators, substrates or releasers.
References
1.Aggarwal S, Mortensen OV. Curr Protoc Pharmacol. 2017;79:12.16.1–12.16.17.
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