*HOW ARE NEUROTRANSMITTERS REMOVED FROM THE BODY*
Usually after a neurotransmitter molecule has been recognized by a post-synaptic receptor, it is released back into the synaptic cleft. Once in the synapse, it must be quickly removed or chemically inactivated in order to prevent constant stimulation of the post-synaptic cell and an excessive firing of action potentials.
Some neurotransmitters are removed from the synaptic cleft by special transporter proteins on the pre-synaptic membrane. These transporter proteins carry the neurotransmitter back into the pre-synaptic cell, where it is either re-packaged into a vesicle and stored until it is once again needed to transmit a chemical message, or broken down by enzymes. Serotonin is one neurotransmitter that gets recycled in this way. Serotonin, a small-molecule neurotransmitter found in many areas throughout the brain, is involved in a wide range of behaviors, including sleep, appetite, memory, sexual behavior, neuroendocrine function, and mood.
Not all neurotransmitters are recycled by the presynaptic cell. Neuropeptide neurotransmitters merely quickly diffuse away from the receptors into the surrounding medium. 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. Acetylcholine (ACh), an excitatory small-molecule neurotransmitter found at various locations throughout the central and peripheral nervous systems and at all neuromuscular junctions, is composed of acetate and choline. AChE breaks ACh into its component parts; acetate and choline. After hydrolysis, acetate quickly diffuses into the surrounding medium, while choline gets taken back into the presynaptic cell by a high affinity choline uptake (HACU) system. Choline is then recycled by the pre-synaptic cell for use in the synthesis of more ACh.
*Bact to the question*
How are neurotransmitter removed or terminated in the body?
There are three mechanisms for the removal of neurotransmitter: ➡Diffusion
➡Degradation, and
➡Reuptake.
*Diffusion*
Diffusive processes affect all molecules, not just neurotransmitters: all else being equal, an ensemble of particles will, over time, decrease in its order. Having more particles in the cleft than outside is a highly-ordered state, and so the particles move until the concentrations are equal.
When neurotransmitter has diffused away, that information disappears.
For lipid-soluble neurotransmitters, like nitric oxide or the endocannabinoids, this is the only mechanism.
*Degradation*
Neurotransmitters can also be broken down.
The classic example of this mechanism is the breakdown of the neurotransmitter acetylcholine into its constituent parts, acetate and choline, by the enzyme acetylcholinesterase (AChE).
Persons discussing this process are obligated by intergalactic law to mention that acetylcholinesterase is one of the fastest enzymes in the body: when AChE catalyzes the degradation reaction, the rate is limited only by how quickly the substrate can diffuse into and out of the enzyme. The reaction itself takes a negligible amount of time.
Peptide neurotransmitters, or neurotransmitters made of short chains of amino acids, are also broken down outside of the cell. This process, however, is general to all small peptides: from the perspective of the body, loose peptides are to be presumed guilty and shot on sight, since they are likely to be a toxin.
*Reuptake*
Neurotransmitters in the synapse can also be recycled directly.
This mechanism is common to all of the classical “small-molecule” neurotransmitters except acetylcholine, i.e. to all of the neurotransmitters you’re likely to think of off the top of your head.
Examples include:
Glutamate, GABA, Dopamine, Epinephrine and norepinephrine
In each case, the pre-synaptic neuron (or possibly a glial comrade-in-arms) expresses a reuptake transporter, or a protein that pushes the neurotransmitter against its concentration gradient and ferries it across the cell membrane.
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