Q:
Where is serotonin mostly found in the body?

A:
90% of all serotonin is found in the gut, in enterochromaffin cells (largely) and in neurones of the enteric nervous system.

Q:
True or false? Platelets synthesise serotonin.

A:
False. Platelets merely take up serotonin during their passage through the gut.

Q:
True or false? Only 0.1% of serotonin is found in the central nervous system.

A:
False. 4-5% of serotonin is found in the central nervous system.

Q:
Regarding serotonin 1A receptors:
Where are they located?
What are their main effects?
What is their second messenger?
What are their antagonists?

A:
Location: Brain
Main Effects: Neuronal inhibition, sleep, feeding, anxiety, thermoregulation
Second Messenger: Decrease in adenylate cyclase, decrease in cAMP
Antagonists: Spiperone, ergotamine (partial agonist)

Q:
Regarding serotonin 1B receptors:
Where are they located?
What are their main effects?
What is their second messenger?
What are their antagonists?

A:
Location: Brain
Main Effects: Presynaptic inhibition, behavioural effects (sleep, feeding, anxiety)
Second Messenger: Decrease in adenylate cyclase, decrease in cAMP
Antagonists: Ergotamine (partial agonist)

Q:
Regarding serotonin 1D receptors:
Where are they located?
What are their main effects?
What is their second messenger?
What are their agonists?
What are their antagonists?

A:
Location: Blood vessels of the brain
Main Effects: Cerebral vasoconstriction, behavioural
Second Messenger: Decrease in adenylate cyclase, decrease in cAMP
Agonists: Sumatriptan
Antagonists: Ergotamine (partial agonist)

Q:
Regarding serotonin 2A receptors:
Where are they located?
What are their main effects?
What is their second messenger?
What are their agonists?
What are their antagonists?

A:
Location: Brain, platelets, smooth muscle
Main Effects: Neuronal excitation, behavioural, platelet aggregation, contraction of the gut
Second Messenger: Increase in phospholipase C (increase in IP3, DAG)
Agonists: LSD in brain
Antagonists: Ketanserine, Methysergide, LSD in body

Q:
Regarding serotonin 2B receptors:
Where are they located?
What are their main effects?
What is their second messenger?

A:
Location: Gastric fundus
Main Effects: Contraction
Second Messenger: Increase in phospholipase C (increase in IP3, DAG)

Q:
Regarding serotonin 2C receptors:
Where are they located?
What are their main effects?
What is their second messenger?
What are their agonists?
What are their antagonists?

A:
Location: Choroid plexus
Main Effects: CSF secretion
Second Messenger: Increase in phospholipase C (increase in IP3, DAG)
Agonists: LSD
Antagonists: Methysergide

Q:
Regarding serotonin 3 receptors:
Where are they located?
What are their main effects?
What is their second messenger?
What are their agonists?
What are their antagonists?

A:
Location: CNS, PNS
Main Effects: excitatory, behavioural, emesis, anxiety
Second Messenger: None - ion channel linked
Agonists: Cl-phenyl biguanide
Antagonists: Ondansteron

Q:
Regarding serotonin 4 receptors:
Where are they located?
What are their main effects?
What is their second messenger?
What are their agonists?

A:
Location: Gut, brain
Main Effects: excitation
Second Messenger: Increase in in cAMP
Agonists: Metoclopramide

Q:
Regarding serotonin 5 and 6 receptors:
Where are they located?
What are their main effects?

A:
Location: Brain
Main Effects: Unknown

Q:
Regarding serotonin 7 receptors:
Where are they located?
What are their main effects?

A:
Location: Brain, gut
Main Effects: unknown

Q:
True or false? All 5-HT receptor are G protein coupled.

A:
False. All 5-HT receptor are G protein coupled except fot 5-HT3 recptors which are ligand gated cation channels.

Q:
True or false? After serotonin is released into the synaptic cleft from presynaptic vesicles is inactivated by 5-HT esterases.

A:
False. Serotonin has a presynaptic uptake site and is recycled.

Q:
What does SSRI stand for?

A:
Selective Serotonin Re-uptake Inhibitor.

Q:
True or false? Sleep, cognition, sensory perception, appetite, sexual behaviour, temperature regulation, autonomic regulation and hormone secretion are all affected by serotonin.

A:
True.

Q:
What is the major effect of serotonin in the gastrointestinal tract?

A:
* Serotonin causes increased gastrointestinal motility and contraction.
   - Direct effect on smooth muscle cells
   - Indirect excitatory effect on enteric neurones

(The peristaltic reflex is partly mediated by 5-HT release from chromaffin cells.)

Q:
What is the major effect of serotonin on smooth muscle?

A:
* In the gastrointestinal tract serotonin causes increased motility and contraction.
* Elsewhere in the body smooth muscle is also contracted by serotonin but only to a minor extent.

Q:
What is the major effect of serotonin on platelets?

A:
* Aggregation (via 5-HT2A  receptors)

Note: Platelets that aggregate and collect vessels release more serotonin. (A positive feedback loop).

Q:
What is the major effect of serotonin on blood vessels?

A:
The effects of serotonin on blood vessels can vary.

* Serotonin cause constriction of smooth muscle cells (mediated by 5-HT 2A receptor).
* Serotonin causes vasodilation by acting on 5-HT 1 receptors (releasing NO and inhibiting release of noradrenaline)

Large vessels both arteries and veins tend to be constricted by 5-HT. 
Smaller vessels tend to be dilated by 5-HT.
Vessels with damaged endothelium are constricted by 5-HT.

Q:
What is the major effect of serotonin on peripheral nerve endings?

A:
* Pain (nociceptive nerve endings stimulated)
* Complex cardiovascular events

Q:
What is the effect of systemic administration of serotonin  on blood pressure?

A:
Blood pressure usually first rises because of the constriction of large vessels then falls due to arteriolar dilatation.

Q:
What (in summary) is 'Carcinod Syndrome'?

A:
* Rare disorder associated with malignant tumours of enterochromaffin cells
* Tumours secrete a variety of hormones such as 5-HT, substance P, prostaglandins and bradykinins
* Symptoms include flushing, diarhoea, bronchoconstriction, hypotension, heart valve stenosis, episodic hypertension, etc.
* Diagnosed by measuring 5-HIAA levels in urine (raised in this syndrome)
* Recommended treatment with the somatostatin analogue, Octreotide. (Supresses secretion of all mediators, not just 5-HT).

Q:
What is the main metabolite of serotonin? 

A:
5-HIAA.

Q:
What evidence is there to suggest serotonin is involved in the pathogenesis of migraines?

A:
* There is a sharp increase in the urinary excretion of the main 5-HT metabolite, 5-HIAA, during the attack. 
* The blood concentration of 5-HT falls, probably because of depletion of platelet 5-HT.
* Many of the drugs that are effective in treating migraine are 5-HT receptor agonists or antagonists. 

Q:
What are the clinical uses of 5-HT 1D agonists such as Sumatriptan and Ergotamine (partial agonist)?

A:
Migraine.

Q:
What are the clinical uses of 5-HT uptake inhibitors such as fluoxetine (prozac)?

A:
* Depression
* Obsessive compulsive disorders

Q:
What are the clinical uses of 5-HT 3 antagonists such as Ondansetron?

A:
Antiemetic (particularly useful for controlling chemotherapy induced emesis).

Q:
What are the clinical uses of 5-HT 2 antagonists such as Methysegide?

A:
* Migraine prophylaxis
* Control of symptoms in carcinoid tumours

Q:
What are the clinical uses of 5-HT 4 agonists such as cisparide?

A:
GI disorders du to their ability to stimulate coordinated peristaltic activity.

Q:
What are the clinical uses of 5-HT 1a partial agonists such as buspirone?

A:
* Anxiety
* Deression