Lecture 5 - Serotonin Flashcards
Where is serotonin found in the body?
90% in the gut
10% in the CNS, mostly in the midbrain
Describe how serotonin is synthesised
Tryptophan found in dairy, meat and fish, taken into serotonergic neurons by the aromatic L-amino acid transporter, in cotransportation with Na
Converted into 5-hydroxytryptophan by tryptophan hydroxylase
Converted into serotonin by dopa decarboxylase
Describe how serotonin is degraded
Degraded firstly by monoamine oxidase
Degraded further by aldehyde dehydrogenase to produce 5-HIAA, which is excreted in the urine
What are the types of tryptophan hydroxylase and where is it expressed?
Tph1a, Tph1b and Tph2
Found in both the CNS and PNS
Differentially expressed e.g. Tph2 exclusively found in the brain
Midbrain is most important area of localisation
How many subtypes of the serotonin receptor are there and what type of receptor is each?
5HT(1-7)
All are GPCRs except 5HT3 which is a ligand gated ion channel permeable to sodium and potassium ions
What g-protein is each serotonin receptor linked to?
5HT1(a,b,d,e,f) and 5HT5(a,b) = Gi/o
5HT2(a,b,c) = Gq
5HT(4,6,7) = Gs
Describe the process of serotonin reuptake and transport into vesicles
Reuptaken into the neuron by 5HT transporters (also known as SERT), cotransported with sodium
Taken into vesicles by VMAT transporter in exchange for H+ ions
Which serotonin receptors are inhibitory autoreceptors?
5HT1(a,b,d)
Present presynaptically
Reduce further release of serotonin
How do SSRIs work?
Name some examples
Block the 5HT transporter (SERT) from reuptaking serotonin, so increases bioavailability in the synaptic cleft
Fluoxetine, Citalopram, Escitalopram, Paroxetine, Sertraline, Fluvoxamine
What is an advantage and disadvantage of SSRIs?
Targeted to 5HT transport - does not affect NA or dopamine bioavailability
Have many side effects - GI related and insomnia
What disorders can SSRIs be used to treat?
Major depressive disorder Bulimia Nervosa OCD Generalised anxiety disorder PTSD Social anxiety disorder
Why do SSRIs take a couple of weeks to start working?
Increased serotonin bioavailability
Increased activation of 5-HT1a inhibitory autoreceptor
Inhibition of further serotonin release
After chronic use, the 5-HT1a receptor desensitises and the therapeutic threshold is reached
Where in the brain are 5-HT1a receptors expressed?
Brain stem Hippocampus Amygdala Hypothalamus Entorhinal cortex
How can medications targeting serotonin receptors be used to treat migraines?
What are these types of medications called?
Alkaloids and triptans Agonise the 5HT1(b,d,f) receptors Reduced cAMP Reduced release of vasoactive peptides Prevents vasodilation
What are the side effects of migraine medication and why?
CVD, hypertension, cerebrovascular disease
Because 5HT1b is also expressed on peripheral smooth muscle, so agonising this also causes vasoconstriction here
