Serotonin Flashcards
Why is serotonin called serotonin ?
Because it was found in blood serum during clotting
“Ser” for it being in serum
“Tonin” for its vascular effects
What groups make up serotonin ?
Indole group and an amine group
Where is serotonin present ?
As a neurotransmitter in PNS and CNS
As a local hormone in peripheral vascular system
90% is in the wall of the intestine
In blood
Only 1-2% in the CNS - midbrain
Also in pineal gland as it is a precursor melatonin
What amino acid can be converted into serotonin and how do we get it?
Tryptophan
L-tryptophan is the only substance in normal diet
Found in bananas, milk and chocolate
What is eosinophilia myalgia ?
Caused by taking dietary supplements of l-tryptophan
Incurable and sometimes fatal neurological syndrome
How is serotonin made ?
L-tryptophan converted by L-tryptophan -5-mo oxygenase tryptophan hydroxylase to 5-hydroxy-L-tryptophan
Then it’s converted to serotonin by 5-hydroxytryptophan decarboxylase
How is serotonin stored ?
Stored on small clear vesicles in presynaptic vesicle
25% is in ready releasable pool
75% is in storage pool
After the release of serotonin what happens to it ?
Taken up by the nerve terminal by SERT transporter which is dependent upon sodium gradient and have a 12 transmembrane domain
Protonated serotonin, sodium ion and chloride ion bind to the transporter and induces a conformational ch age causing serotonin molecule to be inserted into cytoplasm
Potassium ion in the cytoplasm binds to the tranpsorter to reorient ate the transporter
What is the effect of P-chloroamphetamine and fenfluramine on the uptake transporter ?
They can bind to it and cause the release of any serotonin in the cytosol
What effect do SSRIs have on the uptake transporter ?
Prevent the reuptake of serotonin to enhance its effects
E.g reserpine and tetrabenazine
What is fenfluramine used for and why ?
Weight control drug
Because increased levels of serotonin rescue appetite
What does ecstasy do to the body ?
Inhibits uptake of serotonin in the brain
Causes increased heart beat, emotional high and increased energy levels- euphoria
How is serotonin metabolised ?
Converted to 5-HIA by MAO
5-HIA converted to 5-HIAA by aldehyde dehydrogenase
5-HIAA is excreted in CSF
Serotonin can also be converted to melatonin by methylation or acetylation
Is MAO-A or MAO-B more effective at metabolising. Serotonin and which is present in serotonin neurones ?
MAO-A is more effective yet MAO-B is present in serotonergic neurones
What are examples of serotonin neurotoxins ?
5,6- DHT- used in research
5,7-DHT- taken up by SERT
What is the purpose of amphetamines in the serotonin system ?
Act as highly selective serotonin neurotoxins following chronic admin of PCA, fenfluramine and ecstasy
What are the 2 main ascending serotonergic pathways from midbrain raphe nuclei ?
Dorsal periventricular pathway
Ventral tegmental pathway