After neurotransmitters have been released into the synaptic cleft, they act upon postsynaptic receptors, as covered in the previous chapters. That action must be terminated in order for proper neuronal communication to continue. This is accomplished mainly through two processes: neurotransmitter transport and/or degradation. Transport physically removes the neurotransmitter molecule from the synaptic cleft. Degradation breaks down the neurotransmitter molecule by enzyme activity. Show AcetylcholineAcetylcholine action is terminated by acetylcholinesterase, an enzyme present in the synaptic cleft. Acetylcholinesterase degrades acetylcholine into choline and acetate molecules. Choline is then transported back into the presynaptic terminal and used in the synthesis of new acetylcholine.  GlutamateGlutamate action is terminated by two mechanisms. Reuptake of glutamate molecules into the presynaptic terminal can occur, or glutamate can be transported into nearby glial cells. The excitatory amino acid transporters are sodium co-transporters and use the sodium electrochemical gradient to drive neurotransmitter transport. Within glial cells, glutamate is converted into glutamine by glutamine synthetase. Glutamine is then transported out of the glial cell and back into the presynaptic terminal for use in future glutamate synthesis. If glutamate is transported back into the presynaptic terminal, it can be repackaged in synaptic vesicles. GABA and GlycineLike glutamate, GABA and glycine action are terminated by either reuptake into the presynaptic terminal and packaging in synaptic vesicles or through transport into glial cells where breakdown can occur. The GABA and glycine transporter also use the sodium electrochemical gradient to drive the movement of the transmitter across the membrane. DopamineDopamine action is terminated by reuptake into the presynaptic terminal via the dopamine transporter (DAT). Once inside the cell, dopamine is either degraded via the actions of either monoamine oxidase (MAO) or catechol-O-methyltransferase (COMT), or it is repackaged into vesicles. NorepinephrineNorepinephrine follows the same pathway as dopamine. Reuptake into the presynaptic terminal occurs via the norepinephrine transporter (NET), and then the transmitter is either degraded within the cell by MAO or COMT or repackaged into synaptic vesicles. SerotoninLike the other monoamines, serotonin is transported back into the presynaptic terminal via the serotonin transporter (SERT). The difference between serotonin and the catecholamines dopamine and norepinephrine is that monoamine oxidase is the only enzyme used for degradation.
Test Yourself!Video LectureWhat breaks down neurotransmitters in the synaptic cleft?One important neurotransmitter, acetylcholine, has a specialized enzyme for inactivation right in the synaptic cleft called acetylcholinesterase (AChE. AChE is an enzyme present at all cholinergic synapses which serves to inactivate acetylcholine by hydrolysis.
What is acetylcholine destroyed by?Acetylcholine is rapidly destroyed by the enzyme acetylcholinesterase and thus is effective only briefly. Inhibitors of the enzyme (drugs known as anticholinesterases) prolong the lifetime of acetylcholine.
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