Serotonin Flashcards
What type of neurotransmitter is Serotonin?
Monoamine neurotransmitter alongside Noradrenaline and Dopamine.
Where is 5-HT found?
In the gut
In platelets and has a role in platelet aggregation
In the CNS
Describe the synthesis pathway of Serotonin.
Serotonin is derived from the precursor Tryptophan which is derived from our diet. Tryptophan is converted by two enzymes within the cascade to Serotonin. The first Tryptophan hydroxylase converts it to 5-hydroxytryptophan before being converted by L-aromatic acid decarboxylase (also known as dopa decarboxylase or 5-Hydroxytryptophan decarboxylase) to 5-Hydroxytryptamine (Serotonin). The neurotransmitter is then packaged into synaptic vesicles and used.
Describe the metabolism of Serotonin.
Monoamine oxidase present intercellularly is responsible for the degradation of 5-Hydroxytryptamine (Serotonin) into an intermediate which is then further metabolised by aldehyde dehydrogenase into 5-Hydroxyindoleacetic acid which is then excreted.
Describe the process of serotonergic neurotransmission.
Within the nerve terminal, tyrpothophan is broken down into 5-Hydroxytryptamine (Serotonin). Vesicular monoamine transporter (VMAT) facilitates the loading of Serotonin into synaptic vesicles. Similar to the release of other neurotransmitters, depolarisation of the pre-synaptic terminal leads to an increase in Ca2+ permeability. Calcium ion influx then facilitates Ca2+ dependent exocytosis controlling the release of 5-HT into the synaptic cleft. Serotonin is then able to act on their post-synaptic receptors.
How does Serotonin re-uptake occur?
The reuptake of Serotonin from the synaptic cleft to the pre-synaptic serotonergic neuron is facilitated by the presence of the monoamine transporter protein SERT encoded by the SLC6A4 gene. Also known as sodium-dependent serotonin transporter it is a 12 transmembrane domain symporter that relies on the presence of sodium as a co-transporter ion.
What are serotonergic neurons?
Any neuron that uses 5-HT (Serotonin) as a neurotransmitter.
Where are serotonergic neurons specifically found?
Their cell bodies lie within the Ralphe nucleus and are able to project to different areas within the brain.
They have a similar distribution to noradrenergic neurons.
Which physiological processes is 5-HT involved in?
Sleep
Appetite
Pain
Thermoregulation
Mood
What type of receptors are Serotonin receptors?
14 known 5-HT receptors and all but one are GPCR.
5-HT3 is a ligand gated ion channel
What are the seven different types of Serotonin receptor?
Seven different types:
◦ 5-HT1 receptors (1A, 1B, 1D, 1E, 1F)
◦ 5-HT2 receptors (2A, 2B, 2C)
◦ 5-HT4, 5-HT5A, 5-HT6 and 5-HT7
receptors
Categorised based on the G-protein they couple to and their downstream signalling response.
What is the signalling pathways for 5-HT1 receptors?
As all 5-HT1 receptors (1A, 1B, 1D, 1E, 1F) are GPCRs they all couple to the inhibitory G protein Gi/G0 which when activated, inactivates adenylyl cyclase, decreasing cyclic AMP levels and may modulate calcium channels. This results in an overall inhibitory effect.
Specifically 5-HT1A when activated initiates a downstream signalling cascade which causes neuronal inhibition whereas 5-HT1B causes presynaptic inhibition.
Where is 5-HT1A located?
Chiefly in the CNS
Where is 5-HT1B located?
CNS
Vascular smooth muscle
Where is 5-HT1D located?
CNS
Blood vessels
Where is 5-HT1E located?
CNS
Where is 5-HT1F located?
CNS
Uterus
Heart
GI tract
What is the signalling pathways for 5-HT2 receptors?
As all 5-HT2 receptors (2A, 2B, 2C) are GPCRs they all couple to the G-protein Gaq/11 to regulate the activity of phospholipase C resulting in an increase in IP3 and Ca2+ causing neuronal excitation.
5-HT2A specifically when activated initiates a downstream signalling pathway which leads to neuronal excitation as it is expressed in the CNS.
Where is 5-HT2A located?
CNS
PNS
Smooth muscle
Platelets
Where is 5-HT2B located?
Gastric fundus
Where is 5-HT2C located?
CNS
Lymphocytes
Describe the signalling pathway of 5-HT3A.
As a ligand gated ion channel which is cation selective and mediates neuronal depolarization and excitation within the central and peripheral nervous systems.
The 5-HT3 receptor consists of 5 subunits centralised around the central ion conducting pore and is permeable to sodium, potassium and calcium ions. Upon serotonin binding the pore opens and there is an inward current of sodium and potassium ions resulting in neuronal excitation (maybe due to depolarisation which then increase permeability to calcium inducing Ca2+ dependent exocytosis of neurotransmitters).
Where is 5-HT3A located?
CNS
PNS
Describe the signalling pathway of 5-HT4, 5A, 6 and 7.
All couple to Gas which upon activation, activates adenylyl cyclase in turn increasing levels of cAMP causing neuronal excitation.
