Neurotransmitter : Overview and Functions

What are Neurotransmitters?  How do they affect your life?

Just like hormones govern many chemical functions in the body, the brain's chemical functions are governed by messengers called neurotransmitters.

Fig. Neurosynaptic transmission

A neurotransmitter is a chemical messenger used by neurons (nerve cells) to communicate in one direction with other neurons. These neurotransmitters are either excitatory or inhibitory. Each cell receives its instructions through nerve processes called dendrites and it passes on instructions to the next cell through its axon. The gap between the axon of one cell and the dendrite of the next is called a synapse.

Special molecules in the dendrite are called receptors. They are shaped to receive only one type of neurotransmitter, which fits it like a key in a lock. The result is that if an excitatory
neurotransmitter reaches the specific receptor, the cell tends to fire. If an inhibitory neurotransmitter reaches the receptor, the cell does not fire.

If neurotransmitters of either type are in short supply, or if they are blocked from reaching their proper receptors, (as a result of either genetics and/or chemical use) cell function tends to be abnormal. The lack of neurotransmitter function then results in maladaptive behavior.

The human brain is very capable of automatically manufacturing the quantity of chemicals it needs IF it is given the raw materials (nutrients from foods) to do so. However, normal diet does not supply enough of the raw materials the brain needs to manufacture the needed level of neurotransmitters. Additionally, stress, worry, chemical use, poor nutrition, pollution and other factors of modern life are known to deplete neurotransmitter levels.

In order to ingest the required amount of food to provide the necessary amount of amino acids needed to maintain normal neurotransmitter levels we would have to eat each day:

• Several pounds of fish
• Gallons of whole milk,
• Platters of cheese and turkey

Not only is this impractical it is impossible, so therefore another source of nutritional support is necessary so we do not gain hundreds of pounds.

Next we will look at a few of the more familiar neurotransmitters and their function.

Neurotransmitter Functions

Neurotransmitters are the chemicals that allow communication to occur in the brain. Different neurotransmitters allow and/or produce different functions. We can link various thinking, feeling and behavioral actions and states to various transmitters.

We discussed earlier there is a balance of these neurotransmitters. What happens if we become deficient or have too much of one or more of these? What causes these interruptions to the natural balance? How can we compensate and help our body rebuild and rebalance? 

Transmitter Molecule	Transmitter Class	Derived from	Receptors / Activities / Comments
Acetylcholine		Choline	functions in both the CNS and the PNS; receptors are cholinergic; 2 receptor classes: muscarinic (metabotropic) and nicotinic (ionotropic); within the periphery ACh is the major transmitter of the autonomic nervous system where it activates muscles; within the brain its major effects are inhibitory or anti-excitatory; its actions in cardiac tissue are also inhibitory
GABA	amino acid	Glutamate	major inhibitory neurotransmitter in the CNS; also exerts effects in the periphery; binds to two classes of receptor termed GABAA (ionotropic) and GABAB(metabotropic)
Glutamate	amino acid		most abundant excitatory neurotransmitter in the CNS; glutamate binds to the metabotropic glutamate receptors (mGluRs) of which there are eight (mGluR1–mGluR8) divided into three families; glutamate also binds to several ionotropic receptors including the N-methyl-D-asparatate (NMDA) receptor (NMDAR), the kainate receptors (KAR), and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (AMPAR)
Aspartate	amino acid		stimulates the NMDA receptor but not as strongly as glutamate
Glycine	amino acid		inhibitory neurotransmitter in the CNS primarily within the brainstem, spinal cord, and retina; binds to glycine receptors (GlyR) which are ionotropic; there are two separate subunit proteins of each GlyR (α and β) that combine in various ways to generate a pentameric structure; there are four α-subunit genes (α1–4) and one β-subunit gene; the primary adult form of GlyR is composed of three α1 subunits and two β subunits; is also a required co-agonist with glutamate on NMDA receptors and in this capacity exerts an excitatory effect
Histamine	diamine	histidine	produced by mast cells, basophils, enterochromaffin-like cells (ECL) of the stomach, and hypothalamus; within the gut histamine stimulates gastric parietal cells to secrete acid; released from mast cells when allergens bind to IgE-antibody complexes; there are four histamine receptors (H1–H4) all of which are GPCRs
Serotonin 5-hydroxytryptamine (5-HT)	monoamine	tryptophan	most abundantly expressed in enterochromaffin cells of the gut where it regulates motility, also found in the CNS and platelets; released from activated platelets where it stimulates further activation propagating role of platelet aggregation in coagulation; in the CNS 5-HT regulates mood, appetite, sleep, memory and learning; selective serotonin re-uptake inhibitors (SSRIs) used in the treatment of depression
Epinephrine synthesis pathway	monoamine	tyrosine	catecholamine neurotransmitter and hormone; binds to both α- and β-adrenergic receptors (GPCRs); produced in the adrenal medulla and some CNS cells; primary hormone of the fight-or-flight response of the sympathetic nervous system; is a major regulator of metabolic processes in numerous tissues; regulates heart rate, induces vascoconstriction and bronchodilation
Norepinephrine synthesis pathway	monoamine	tyrosine	catecholamine neurotransmitter and hormone; binds to both α- and β-adrenergic receptors (GPCRs); produced in CNS by sympathetic nerves; major neurotransmitter function is in regulation of cardiac chronotropic (rate) function; functions along with epinephrine in the fight-or-flight response; involved in adaptive thermogenesis in brown adipose tissue (BAT)
Dopamine synthesis pathway	monoamine	tyrosine	within the CNS dopamine plays a major role in reward-motivated behavior such as feeding and drug-seeking behaviors; also involved in motor control; in the periphery dopamine regulates the release of several hormones such as insulin from the pancreas and norepinephrine from blood vessels; functions by binding to a family of dopaminergic receptors (GPCRs)
Adenosine	other	ATP	is an inhibitory neurotransmitter within the CNS, suppresses arousal thus promoting sleep; within the periphery adenosine exerts anti-inflammatory actions, induces bronchospasm in the lungs, and within the heart where it affects the cardiac conduciton system; adenosine binds to a family of adenosine receptors (GPCRs) identified as A1, A2A, A2B, and A3
ATP	other		as a neurotransmitter ATP is released from sympathetic, sensory and enteric nerves; binds to P2Y12 which is a member of the purinergic family of GPCRs (metabotropic receptors of which there are 12 genes in humans: P2Y1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14; P2Y12 is primarily expressed on the surface of platelets; also binds to the ionotropic family of purinergic receptors (P2X) which consists of seven members (P2X1–7); these receptors modulate synaptic transmission throughout the CNS, PNS, and autonomic nervous system; in the periphery the P2X receptors activate contractile activity of various muscle types
Nitric oxide, NO	gas	arginine	endothelial cells, phagocytic cells, CNS, gastrointestinal tract; binds to and activates soluble guanylate cyclase, oxidizes iron-containing proteins, nitrosylates protein sulfhydryl groups

This is all good information, but exactly what are neurotransmitters?

Neurotransmitters are small molecules whose function is to transmit nerve signals (impulses) from one nerve cell (neuron) to another. Neurotransmitters are chemical messengers which neurons use to tell other neurons that they have received an impulse. There are many different neurotransmitters - some trigger the receiving neuron to send an impulse and some stop it from doing so.

See this simplified diagram of a neuron:

Fig. Neurons (Courtesy : http://www.victorie-inc.us)

Nerve impulses always flow in one direction - from the branched extensions called dendrites, down the neuron to the presynaptic terminals. The join between the presynaptic terminals of one neuron and the dendrites of another is called the synapse. The two neurons do not actually touch each other but are separated by a space called the synaptic cleft. When a nerve impulse arrives at a presynaptic terminal it causes neurotransmitters to be released into the synaptic cleft. The neurotransmitters then bind with special "postsynaptic receptors" in the dendrites of the receiving neuron. When a postsynaptic receptor receives a neurotransmitter it can either cause a nerve impulse to travel down the neuron or it can inhibit a nerve impulse depending on the neurotransmitter released.

Neurotransmitters which propagate nerve impulses in the receiving neuron are called excitatory neurotransmitters. Those which inhibit nerve impulses are called inhibitory neurotransmitters.

Neurotransmitters are sythesized in the cell body (the soma) and migrate down the axon to the presynaptic terminals. Here they are stored in little packets called vesicles which fuse with the synaptic membrane. When a depolarizing current (the action potential) is received, these vesicles release their contents into the synaptic cleft.

Many different substances effect the transmission of nerve impulses across the synapse and many of these are falsely called neurotransmitters. To be a neurotransmitter a substance must:

• be synthezised within neurons
• be released from the presynaptic terminal in response to an action potential (essentially a nerve impulse).
• cause a biological effect in the postsynaptic receptors.
• a mechanism must exist to inactivate or remove the transmitter from the receptor

Neurotransmitters activate receptors by "sticking" to them and thus preventing other neurotransmitters from activating them. Inactivation of the transmitter happens in one of three ways:

• reabsorption of the neurotransmitter into the neuron. This is known as reuptake and is the normal process.
• destruction of the neurotransmitter with special chemicals called enzymes. This is known as enzymatic degradation.
• by the neurotransmitter becoming deteched from the receptor and drifting out of the synaptic cleft. This is known as diffusion.

Substances that effect neurotransmission but are not neurotransmitters can be broadly divided into two categories - agonists and antagonists. Agonists make transmission of nerve impulses more likely. They do this in a number of ways including preventing reuptake (cocaine works this way), actually triggering the receptor themselves (nicotine works this way) and by making the receptor more responsive (a lot of anti-anxiety drugs work like this). Antagonists do the opposite - they interfere with nerve transmission across the synapse sometimes by blocking receptor sites (many spider and snake venoms work this way) and sometimes by preventing release of the neurotransmitter from the presynaptic terminal (many anti-psychotic drugs operate like this).

Source:

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