POP Histamine lecture part 1

What is histamine?

Histamine is a small amine that acts as a local hormone and neurotransmitter involved in allergy, inflammation, gastric acid secretion, and the CNS 🧠🩸

What type of molecule is histamine?

Histamine is a biogenic amine t (~100 Da) that mainly acts locally rather than as a circulating hormone 🔬

What is the precursor of histamine?

Histamine is synthesised from the amino acid histidine 🧬

Describe the synthesis of histamine

Histidine is converted into histamine by the enzyme histidine decarboxylase, which removes the carboxyl (–COOH) group ➡️ CO₂ is released ⚙️

Where is histamine synthesised?

Histamine is synthesised mainly in mast cells, gastric mucosa cells, and rapidly growing tissues;

synthesis increases during stress and infection 🚨

Does dietary histamine contribute to body histamine stores?

No. Dietary histamine is rapidly metabolised and does not contribute to the body’s histamine pool ❌🍷

Where is histamine stored?

Histamine (+ enzymes like tryptase and chymase)

is stored mainly in mast cell granules,

bound to heparin (the glue that sticks them together ) 📦

What are mast cells?

Mast cells are long-lived, tissue-resident immune cells that store and release histamine during inflammation 🦠

List the three mechanisms of histamine release

Histamine is released by (1) IgE-dependent mechanisms, (2) receptor-mediated non-IgE mechanisms, and (3) non-specific mechanisms ⚡

Describe IgE-dependent histamine release

Allergen cross links IgE —— > IgE antibodies bind to mast cells ———> causing mast cell degranulation and histamine release → allergy symptoms 🤧

What triggers non-IgE receptor-mediated histamine release?

Bacterial products (e.g. LPS) and complement proteins (C3a, C5a) activate mast cell receptors, causing histamine release during infection 🦠

What causes non-specific histamine release?

Basic drugs (e.g. morphine), tissue trauma, UV radiation, burns, or osmotic changes can directly trigger histamine release 💊🔥

What are the four histamine receptors?

The four histamine receptors are H1, H2, H3, and H4 — all are G-protein-coupled receptors 🔑

Where are H1 receptors found?

H1 receptors are found in blood vessels, smooth muscle, peripheral nerves, and the CNS 🩸🫁

What are the four main actions of histamine via H1 receptors?

H1 activation causes vasodilation, increased vascular permeability, peripheral nerve stimulation (itch/pain), and smooth muscle contraction 🌡️💧😖

How does histamine cause redness and heat?

Histamine causes arteriolar vasodilation via H1 receptors, increasing blood flow to the area → redness and warmth 🔴🔥

How does histamine cause swelling?

Histamine increases vascular permeability, allowing fluid and proteins to leak into tissues, causing swelling (oedema) 💧⬆️

What causes itching and pain in histamine responses?

Histamine stimulates peripheral sensory nerves, leading to itching and pain sensations 😖🧠

What is the wheal-and-flare reaction?

It is a skin response to histamine injection: wheal = swelling, flare = redness, caused by vasodilation and nerve reflexes 🌼

How does histamine affect smooth muscle?

Histamine causes smooth muscle contraction, especially bronchoconstriction in the lungs, which is dangerous in asthma 🫁⚠️

How does histamine affect blood pressure at low doses?

Low doses of histamine dilate arterioles, reduce peripheral resistance, and lower blood pressure ⬇️🩸

What happens with large doses of histamine?

Large doses cause severe hypotension, fluid leakage from capillaries, and can lead to anaphylactic shock 🚑

Where are H2 receptors located?

H2 receptors are mainly found on gastric parietal cells, but also in the heart and some immune cells 🍽️❤️

What is the main action of histamine via H2 receptors?

H2 receptor activation stimulates gastric acid (HCl) secretion in the stomach 🧪

Describe histamine-induced gastric acid secretion

Histamine binds H2 receptors on parietal cells → activates Gs protein → increases cAMP → activates proton pump (H⁺/K⁺ ATPase) → acid secretion 🔄

What is cimetidine?

Cimetidine is an H2 receptor antagonist used to reduce gastric acid secretion in peptic ulcer disease 💊

Why does cimetidine cause drug interactions?

Cimetidine inhibits cytochrome P450 enzymes, slowing drug metabolism and increasing drug effects ⚠️

What are H1 antihistamines used for?

H1 antagonists are used to treat allergies, motion sickness, and as sedatives 🤧😴

Give examples of H1 antihistamines

Mepyramine (older, sedating) and cetirizine (newer, less sedating) 💊

Where are H3 receptors found?

H3 receptors are found mainly in the CNS and regulate histamine release as presynaptic receptors 🧠

What is the role of H3 receptors?

H3 receptors regulate neurotransmitter release and are involved in sleep–wake cycles and alertness 🌙☀️

Where are H4 receptors found?

H4 receptors are found on immune and inflammatory cells 🧬

What is the role of H4 receptors?

H4 receptors regulate cytokine release and inflammation and may be targets for autoimmune disease treatment 🔬

Which diseases are strongly linked to histamine?

Histamine is involved in allergy, asthma, peptic ulcer disease, and anaphylactic shock 🚨