Histamine Flashcards
What are functions of histamine?
Mediates allergic responses
Gastric acid secretion
CNS neurotransmitter
Promotes bronchoconstriction, mucus secretion
Increases permeability
Where is histamine stored?
Mast cells (CT around blood vessels, skin, lung mucosa gut, mouth, nose, eyes) - secretory granules
Histamine generation and storage occur in the epidermis, gastric mucosa, neurons, cells in regenerating tissues
What stimulates degranulation (release of histamine)?
Immunoglobulin (IgE)
Chemicals
Toxins
Basic drugs (D-tubocurarine, morphine)
Trauma
Where are H1 receptors found?
Smooth muscle
Endothelial cells
CNS
What is the G protein associated with H1 receptors? What effect results from stimulation?
Gq
Gq => inc. PLC => more intracellular calcium
Effects:
CONTRACTION
NO release
Neurotransmitter release
Where are H2 receptors found?
Parietal cells in gut/stomach
Mast cells
Vascular SM
Myocardium
What G protein is associated with H2 receptors? What effects does the signal transduction have?
Gs
Gs => inc. cAMP => PKA activity
Effects:
Inc. gastric secretion
SM relaxation
Where are H3 receptors found?
CNS
What does the signal transduction pathway of H3 receptors look like?
Gi/o => dec. cAMP
Where are H4 receptors distributed?
Eosinophils
Neutrophils
Signal transduction pathway of H4 receptors?
Gi/o => dec. cAMP
Inc. intracellular calcium
Which histamine receptors mediate vasodilation in the cardiovascular system?
H1 and H2
Compare vasodilation effects among H1 and H2 receptors
H1 = endothelium H2 = smooth muscle
H1 = NO-dependent H2 = cAMP-dependent
H1 = rapid dilation, short lived H2 = slow dilation, sustained
How do H1 receptors affect capillaries?
Increased post-capillary venule permeability
How do H1 receptor stimulation lead to increased permeability?
Endothelial cell contraction results in disruption of cell-cell junctions, exposing the basement membrane.
This makes vessel more permeable to plasma proteins and fluids, as well as inflammatory cell infiltration.
What is the local CV response induced by histamine?
Erythema
Flare
Wheal
What is the mechanism behind erythema?
H1 and H2 receptors lead to capillary dilation
What is the mechanism behind erythema + flare?
H1 receptors lead to indirect dilation mediated by sensory nerves
What is the mechanism behind the wheal?
H1 receptor leads to receptor-mediated capillary permeability
What are peripheral nerve ending responses from histamine?
Itch, pain, flare in the triple response = H1 receptors
What are respiratory system responses to histamine?
Bronchial SM contraction + increased secretions (H1, DOMINANT) and relaxation via H2
How do histamine and gastric acid secretion relate?
Histamine released from ECL cells in stomach will stimulate parietal cells in the stomach to release gastric acid
Describe histamine release under hormonal and neural control.
Hormonal
Gastrin binds to gastrin/CCK receptors on ECL cells
=> inc. histamine release
Neural
ACh stimulates mAChRs on ECL cells => inc. histamine release
What are the effects of H1 antihistamines?
Block:
Histamine-induced contraction of GI + bronchial SM
Flare + itch response
Histamine-elicited upper respiratory secretions and increases in capillary permeability
Why do H1 antihistamines only partially block histamine-elicited vasodilation?
There are two receptors! H1 and H2
Why do H1 antihistamines have a partial effect on anaphylaxis?
Other mediators are also secreted from mast cells that can also promote anaphylaxis response
What are H1 antihistamine side effects?
Anti-muscarinic side effects:
dry mouth
Dec. nasal/ upper respiratory secretions
Urinary retention
Sedation
Motion sickness, anti-emitic effects (some)
What are therapeutic uses for H1 antihistamines?
Upper respiratory tract allergic symptoms, hay fever, and pollinosis, common cold
Urticaria (allergic CD) - systemically!
Anaphylactic shock - prophylactically!
delayed hypersensitivity reactions
Sedation in OTC sleep medications
Anti-motion sickness
What are therapeutic uses of H2 antihistamines?
Acid-peptic ulcer disease
Zollinger-Ellison syndrome (gastrin-secreting tumor)
Prevention of damage from pulmonary aspiration
Potential anti-inflammatory
