Neurotransmitters - Anatomy & Physiology

Nerve - © fig.cox.miami.edu 2008

Introduction

Neurotransmitters are chemicals that are used to relay, amplify and modulate signals between neurones and cells. They can be classified into two main groups; small-molecule transmitters (SMT) and neuropeptides. SMTs are synthesised within nerve terminals via enzymes that are produced within the cell body. Within most nerve junctions, the terminal membrane of the nerve contains numerous specific transport proteins that facilitate the transport of the majority of the SMTs back into the nerve terminal, effectively recycling the neurotransmitter. Neuropeptides are constructed of around 3 - 40 amio acid molecules that are synthesised within the cell body and are then transported to along the axon to the nerve terminal within vesicles running along microtubules. Neuropeptides are broken down by extracellular enzymes called peptidases once the neurotransmitter has been released. A small proportion of neuropeptides can bind to postsynaptic receptors in the nerve terminal membrane and can be taken up by endocytosis, although the degree of recycling of neuropeptides is lower than that of SMTs.

Types of neurotransmitter

Small-molecule Neurotransmitters

There are two major sub-groups of SMTs; amino acids and biogenic amines. All SMTs play an important role within the central nervous system with the exception of acetylcholine and norepinephrine which both are important within the peripheral nervous system.

Amino Acids

Amino acid glutamate is the most common excitatory SMT in the central nervous system whilst gamma-aminobutyric acid (GABA) is the most common inhibitory SMT. Other amino acid SMTs include aspartate and glycine.

Biogenic Amines

Biogenic amines are synthesised from only several types of amino acids and dependant on which amino acids are used in their formation depends on their classification. Biogenic amines that are derived from the amino acid tyrosine are classified as catecholamines and include the SMTs norepinephrine (noradrenaline), epinephrine (adrenaline) and dopamine. Adrenergic neurons release norepinephrine. The biogenic amines that is dervied from the amino acid tryptophane is called serotonin (5-HT) whilst the SMT derived from histidine is called histamine. Serotonergic neurons release serotonin. Whilst these SMTs are primarily of importance in the central nervous system, norepinephrine is predominantly found in the peripheral nervous system.

Other SMTs

Other common SMTs include acetylcholine (ACh), ATP and nitric oxide (NO). Ach is the most common excitatory neurotransmitter in the peripheral nervous system. Cholinergic neurons release ACh and for example, are found in the neuromuscular junction. ATP, as well as having many important intracellular functions, is an important neurotransmitter and also has an autocrine and paracrine function. All synaptic vesicles released by the terminal membrane of a nerve contain ATP as well as other neurotransmitters, although ATP can only function as a neurotransmitter in it's own right if the post-synpatic terminal membrane contains ATP receptors. These ATP receptors are referred to as purinergic receptors. A pre-synaptic nerve terminal or terminal membrane never releases multiple types of SMT in addition to ATP, although it is common that neuropeptides are released in addition to ATP and SMTs.

Although NO is a neurotransmitter, it's characteristics differ from those discussed above. NO relies on calcium ion activation of the enzyme nitric oxide synthase NOS which is found throughout the nervous system and is the enzyme that is responsible for catalysing NO from the amino acid L-arginine. NO has a very short half life and is highly reactive. It is able to pass easily through lipid membranes. What makes NO differ from the SMTs above is that is can be released in all directions rather than pre-synaptically as per the classical SMTs. Therefore NO is able to act as a signalling pathway for the post-synaptic neuron to affect the pre-synpatic neuron.

These include:

• Acetylcholine (Ach)

• Monoamines - epinephrine (E), norepinephrine (NE), dopamine (DA), serotonin (5-HT) and melatonin.

• Three or four amino acids, depending on exact definition used: primarily glutamic acid, gamma aminobutyric acid (GABA), aspartic acid & glycine.

• Purines -(Adenosine, adenosine triphosphate (ATP), Guanosine triphosphate (GTP) and their derivatives.

• Peptides - vasopressin, somatostatin etc.

• Histamine (HA)

• Single ions - such as synaptically released zinc.

• Gaseous - nitric oxide (NO) and carbon monoxide (CO).

Function

Release of excitatory neurotransmitters from the presynaptic membrane cause channels in the postsynaptic membrane to open and cause an increase in sodium ion concentration within the postsynaptic cell and a decrease in potassium ion concentration. This leads to a depolarisation of the postsynaptic cell, which is propagated further along the axon by an action potential (AP).

Inhibitory neurotransmitters cause hyperpolarization of the postsynaptic cell making it unable to generate an action potential.

Receptors determine the reaction of the neurotransmitter meaning that the same neurotransmitter may cause an excitatory effect on some membranes whilst an inhibitory effect on others e.g ACH can be either excitatory to skeletal muscle cells or inhibitory to both smooth muscle and cardiac muscle.

Actions

Neurotransmitter	Action
Acetylcholine (Ach)	Skeletal muscle movement (sympathetic) Visceral movement (parasympathetic)
Epinephrine	As norepinephrine, produced by adrenal glands.
Norepinephrine	Conciousness (sympathetic).
Dopamine	Addiction, love, motivation.
Seretonin	Emoticon, conciousness, sleep and thermoregulation.
Melatonin	Regulates the onset of sleep and seasonal changes in the body e.g winter weight gain.
ATP	Timing mechanism of G proteins by displacement of ADP.
GTP	Timing mechanism of G proteins by displacement of GDP.
Vasopressin	Metabolic rate, metabolism.
Somatostatin	Inhibits production of other hormones.
Histamine	Gastric secretions increased, dilation of capillaries, constriction of bronchial smooth muscle and decreased blood pressure.
Zinc	Release of neuropeptide Y.
NO	Enlargement of genital organs leading to erection.
CO	Sleep cycle.
Glutamate	Exitatory, found in CNS.
GABA	Inhibitory, found in CNS.
Glycine	Spinal reflexes, motor.

Neurotransmitter systems

See somatic and autonomic nervous systems.

Degradation and elimination

• Acetylcholine is derived from Choline.
• Serotonin [5-Hydroxytryptamine (5-HT)] is derived from Tryptophan.
• GABA is derived from Glutamate.
• Histamine is derived from Histidine.
• Epinephrine, norepinephrine and dopamine are derived from Tyrosine.
• Adenosine is derived from ATP.
• Nitric oxide is derived from Arginine.

Neurotransmitters must be broken down once they reach the post-synaptic cell to end the excitatory or inhibitory signal and prevent over stimulation/perminent inhibition.

• e.g, ACH an excitatory neurotransmitter, is broken down by acetylcholinesterase (AchE).

• Choline is taken up and recycled by the pre-synaptic neuron to synthesize more ACH.

• Other neurotransmitters such as dopamine are able to diffuse away and are eliminated from the body via the kidneys, or destroyed in the liver.