Histamine Flashcards
What is the basic structure of histamine
It is a basic amine formed from histidine (amino acid)
What cell types is histamine found in
Mast cellsBasophilsParacrine (mast-like) cellsNeurones
Where is histamine mainly stored
Mast cells
How is histamine mainly stored
In intracellular granules. In a complex with heparin and an acidic protein
What is the mechanism of histamine release from mast-cells
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.
How many subtypes of histamine are there
4(H1-4)
How does histamine affect signalling mechanisms in cells
Through interaction with GPCRs/ G proteins
How does Histamine H1 affect signalling mechanisms
Activates phospholipase C. Produces IP2 and DAG.Activates PKC and increases cytosolic calcium levels.
How does Histamine H2 affect signalling mechanisms
Activates adenylate cyclase. Produces cAMP. Activates PKA.
How do Histamine H3 and H4 affect signalling mechanisms
Inhibit adenylate cyclase. Decreases cAMP levels. Deactivates PKA
What are the three stages of the histamine response and what causes them
Flush - dilates small arteriolesWheal (lump) - increases permeability of post capillary venules. Allows plasma fluid leakageFlare - acts on sensory nerve terminals. Triggers electrical impulses. Causes release of peptide that causes vasodilation.
What are the main pharmacological effects of histamine
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)
How do the histamine (H1) receptors cause vasodilation
Receptors are on endothelial cell. Can activate:Endothelial NO synthesis/release; causes smooth muscle relaxationEndothelial cell contraction; causes increased vascular permeability. Allows plasma and protein leakage into tissues.
How do the histamine (H2) receptors increase heart rate/force
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.
How do the histamine (H2) receptor mediate acid secretion in the stomach
Receptors on gastric pariental cells cause HCl and pepsin secretion by cells
What role do histamine receptors play in the CNS
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 effectsRegulate release of neurotransmitters (H3)
What is Urticaria
Raised itchy/painful rash that migrates. AKA nettle rash/hives.Type 1 hypersensitivity
What is atopic eczema
Chronic relapsing itchy disease of skin. AKA atopic dermatitisType 1 hypersensitivity
What are H1 receptor antagonists used to treat
Type 1 allergic reactions. E.g. Hay fever, rashes, insect stings/bitesNOT good for bronchial asthma because other factors are involved
Give examples of H1 receptor antagonists
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.
What causes anaphylactic shock and how is it treated
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.
What are the two types of hormone released by the GI tract
Endocrine (e.g. gastrin)Paracrine (e.g. histamine
What are the main stomach secretions
Pepsinogen (from chief/peptic cells)HCl (from parietal cells)
What are the main three stimuli that act on the parietal cells
GastrinAcetylcholineHistamine
How does histamine stimulate parietal cells
Acts on the histamine (H2) receptors. Receptors are more sensitve than H2Rs on blood vessels.
What are the clinical uses of H2 receptor antagonists
Can reduce acid secretion so can treat: peptic ulcer, reflux oesophagitis and Zollinger-Ellison syndromeCan also promote healing of duodenal ulcers
What are thought to cause peptic ulcers
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
How can a H2 receptor antagonist work to treat problems
Competitively inhibit H2 receptors, so inhibit gastric acid secretion. Can reduce acid secretion by 90%+
Give an example of an H2 receptor antagonist
Cimetidine/Ranitidine. (also now nizatidine and famotidine)
Name some side effects of H2 receptor antagonists
Diarrhoea, dizziness, muscle pains, rashes. Sometimes also decreased sexual function and confusion.
What are the specific side effects of the H2R antagonist Cimetidine
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.
