Histamine

Question 1

What is the basic structure of histamine

Answer 1

It is a basic amine formed from histidine (amino acid)

Question 2

What cell types is histamine found in

Answer 2

Mast cells
Basophils
Paracrine (mast-like) cells
Neurones

Question 3

Where is histamine mainly stored

Answer 3

Mast cells

Question 4

How is histamine mainly stored

Answer 4

In intracellular granules. In a complex with heparin and an acidic protein

Question 5

What is the mechanism of histamine release from mast-cells

Answer 5

Allergen bound to IgE on surface of mast-cell. Allergen-IgE interaction leads to cytosolic calcium increase. This promotes exocytosis of secretory granule contents -> Histamine.

Question 6

How many subtypes of histamine are there

Answer 6

4

H1-4

Question 7

How does histamine affect signalling mechanisms in cells

Answer 7

Through interaction with GPCRs/ G proteins

Question 8

How does Histamine H1 affect signalling mechanisms

Answer 8

Activates phospholipase C. Produces IP2 and DAG.

Activates PKC and increases cytosolic calcium levels.

Question 9

How does Histamine H2 affect signalling mechanisms

Answer 9

Activates adenylate cyclase. Produces cAMP. Activates PKA.

Question 10

How do Histamine H3 and H4 affect signalling mechanisms

Answer 10

Inhibit adenylate cyclase. Decreases cAMP levels. Deactivates PKA

Question 11

What are the three stages of the histamine response and what causes them

Answer 11

Flush - dilates small arterioles
Wheal (lump) - increases permeability of post capillary venules. Allows plasma fluid leakage
Flare - acts on sensory nerve terminals. Triggers electrical impulses. Causes release of peptide that causes vasodilation.

Question 12

What are the main pharmacological effects of histamine

Answer 12

Vasodilation (H1+2)
Increased heart rate and force (H2)
Bronchoconstriction (H1)
Smooth muscle constriction (H1)
Acid secretion in stomach (H2)
Regulation of immune cells (H1-4)

Question 13

How do the histamine (H1) receptors cause vasodilation

Answer 13

Receptors are on endothelial cell. Can activate:
Endothelial NO synthesis/release; causes smooth muscle relaxation
Endothelial cell contraction; causes increased vascular permeability. Allows plasma and protein leakage into tissues.

Question 14

How do the histamine (H2) receptors increase heart rate/force

Answer 14

Receptors are on ‘pacemaker’ and muscle cell of heart. Increases firing rate (pacemaker) and contractility (muscle).
Indirectly, vasodilation causes low blood pressure; activates baroreceptor reflexes; increases sympathetic drive on heart.

Question 15

How do the histamine (H2) receptor mediate acid secretion in the stomach

Answer 15

Receptors on gastric pariental cells cause HCl and pepsin secretion by cells

Question 16

What role do histamine receptors play in the CNS

Answer 16

Histamine released from histaminergic nerves in the CNS.
Involved in control of vomiting reflex (+other functions)
Some H1 receptor antagonists have anti-emetic and sedative effects
Regulate release of neurotransmitters (H3)

Question 17

What is Urticaria

Answer 17

Raised itchy/painful rash that migrates. AKA nettle rash/hives.
Type 1 hypersensitivity

Question 18

What is atopic eczema

Answer 18

Chronic relapsing itchy disease of skin. AKA atopic dermatitis
Type 1 hypersensitivity

Question 19

What are H1 receptor antagonists used to treat

Answer 19

Type 1 allergic reactions.
E.g. Hay fever, rashes, insect stings/bites
NOT good for bronchial asthma because other factors are involved

Question 20

Give examples of H1 receptor antagonists

Answer 20

Mepyramine/promethazin. Crosses the blood/brain barrier. Can cause drowsiness because receptors are present in the brain too.
Loratidine/cetirizine.
More modern. Don’t enter CNS.

Question 21

What causes anaphylactic shock and how is it treated

Answer 21

Caused by large-scale histamine release. Causes life-threatening fall in bp.
Treated with adrenaline (causes bronchodilation (beta2 receptors) and vasoconstriction (alpha1 receptors)). H1 receptor antagonist can also be used afterwards.

Question 22

What are the two types of hormone released by the GI tract

Answer 22

Endocrine (e.g. gastrin)

Paracrine (e.g. histamine

Question 23

What are the main stomach secretions

Answer 23

Pepsinogen (from chief/peptic cells)

HCl (from parietal cells)

Question 24

What are the main three stimuli that act on the parietal cells

Answer 24

Gastrin
Acetylcholine
Histamine

Question 25

How does histamine stimulate parietal cells

Answer 25

Acts on the histamine (H2) receptors.

Receptors are more sensitve than H2Rs on blood vessels.

Question 26

What are the clinical uses of H2 receptor antagonists

Answer 26

Can reduce acid secretion so can treat: peptic ulcer, reflux oesophagitis and Zollinger-Ellison syndrome
Can also promote healing of duodenal ulcers

Question 27

What are thought to cause peptic ulcers

Answer 27

Not fully understood. Infection of Helicobacter pylori is a major cause. Also a shift in the balance between mucosal damaging/protecting mechanisms plays a role

Question 28

How can a H2 receptor antagonist work to treat problems

Answer 28

Competitively inhibit H2 receptors, so inhibit gastric acid secretion. Can reduce acid secretion by 90%+

Question 29

Give an example of an H2 receptor antagonist

Answer 29

Cimetidine/Ranitidine. (also now nizatidine and famotidine)

Question 30

Name some side effects of H2 receptor antagonists

Answer 30

Diarrhoea, dizziness, muscle pains, rashes.

Sometimes also decreased sexual function and confusion.

Question 31

What are the specific side effects of the H2R antagonist Cimetidine

Answer 31

Cimetidine inhibits the enzymes in the liver (cytochrome P450) that inactivate many drugs and limit duration/strength of drug action.
Without these enzymes, drug metabolism many be delayed and pharma effects increased.
E.g. Warfarin (anti-coagulant) can cause internal bleeding if used in conjunction.