POP Histamine lecture part 2

What is 5-hydroxytryptamine (5-HT)?

5-HT, also called serotonin, is a biogenic amine neurotransmitter involved in mood, gut motility, and vascular regulation 🧠🦠

Where is 5-HT found in the body?

5-HT is found in the CNS, gastrointestinal tract, and platelets, with most of it stored in the gut 🧠🍽️🩸

What is the main role of 5-HT in the body?

5-HT regulates mood and behaviour, GI motility, and blood vessel tone ⚖️

Which diseases are associated with low 5-HT levels?

Low 5-HT is linked to depression, anxiety, OCD, and panic disorders 😔

Which problems are associated with high 5-HT levels?

High 5-HT can cause anxiety, insomnia, GI disturbance, and serotonin syndrome ⚠️

Describe the structure of 5-HT

5-HT contains an indole ring, an amino group, and a hydroxyl group, which allow it to bind to different receptors 🔬

Describe the synthesis of 5-HT

Tryptophan → (tryptophan hydroxylase) → 5-hydroxytryptophan → (L-aromatic amino acid decarboxylase) → 5-hydroxytryptamine (5-HT) 🧬➡️

What is the precursor of 5-HT?

The amino acid tryptophan is the precursor of serotonin 🧬

Does dietary 5-HT affect body serotonin levels?

No. Dietary 5-HT is rapidly metabolised and does not contribute to the body’s serotonin stores ❌🍌

Describe the metabolism of 5-HT

5-HT is broken down by monoamine oxidase (MAO) and aldehyde dehydrogenase into 5-HIAA, which is excreted in urine 🔄🚽

What is 5-HIAA and why is it important?

5-HIAA is the main metabolite of 5-HT and is measured in urine as a marker of serotonin activity 🧪

Where is most of the body’s 5-HT stored?

About 90% of the body’s serotonin is stored in the gastrointestinal tract 🌍🍽️

Do platelets synthesise 5-HT?

No. Platelets take up 5-HT from the gut circulation and store it but do not synthesise it 🩸

How much serotonin is present in the human body?

The average adult contains only about 10 mg of serotonin ⚖️

Name drugs that alter 5-HT levels

Fenfluramine depletes 5-HT; MDMA causes massive release then depletion; carbohydrate-rich diets indirectly increase 5-HT 💊🍞

How many families of 5-HT receptors are there?

There are 7 families of serotonin receptors, many with multiple subtypes 🔑

Which serotonin receptor is NOT a GPCR?

The 5-HT₃ receptor is a ligand-gated ion channel, not a GPCR ⚡

Where are 5-HT₁ receptors mainly located?

5-HT₁ receptors are mainly found in the CNS, with some on cerebral blood vessels 🧠🩸

What are the effects of 5-HT₁ receptor activation?

Activation causes neural inhibition and vasoconstriction and regulates mood, sleep, feeding, and temperature ❄️🧠

Which drug is a 5-HT₁ agonist used for migraine?

Sumatriptan is a 5-HT₁D (receptor) agonist

used to treat migraine headaches 💊🤕

(causes vasoconstriction in cerebral vessels to improve pain)

Where are 5-HT₂ receptors found?

5-HT₂ receptors are found in both the CNS and peripheral tissues 🧠🌍

How does LSD act on 5-HT₂ receptors?

LSD acts as a 5-HT₂ agonist in the CNS causing hallucinations, but as an antagonist in the periphery 🌈

What is special about 5-HT₃ receptors?

5-HT₃ receptors are ligand-gated ion channels involved in pain signalling and the vomiting reflex ⚡🤮

Which drug blocks 5-HT₃ receptors and why is it used?

ONDANSETRON blocks 5-HT₃ receptors and is used as an anti-emetic in chemotherapy (used to stop vomit) 🤢💊

What is the main role of 5-HT₄ receptors?

5-HT₄ receptors regulate gastrointestinal motility and bowel movement 🚽

Which drug is a 5-HT₄ agonist and what is it used for?

Tegaserod is a 5-HT₄ agonist used to treat IBS and chronic constipation 💊

What part does 5-HT play in migraines? and what’s the evidence

5-HT causes vasoconstriction of cerebral arteries, and increased 5-HIAA is found in migraine patients 🧠🩸

How does 5-HT affect the gut?

5-HT stimulates peristalsis, fluid secretion, nausea, and vomiting by acting on gut smooth muscle and enteric neurons 🍽️➡️

How does 5-HT affect the cardiovascular system?

5-HT causes constriction of large vessels, dilation of arterioles via nitric oxide, and venous constriction leading to flushing ❤️🔄

What is the role of 5-HT in platelets?

5-HT activates 5-HT₂ receptors on platelets, causing aggregation, vasoconstriction, and aiding blood clotting 🩸🩹