Histamine Flashcards
features of histamine and 5-HT
biogenic amines
act as hormones or autacoids
act as neurotransmitters and local hormones in vascular and smooth muscle
histamine associated diseases
allergy
peptic ulcer - break in the stomach lining
what is the N-terminus of histamine
imidazole ring
pKa = 5.74
normally uncharged
outline the synthesis of histamine
histidine decarboxylase converts histidine into histamine
removes the COOH at the C-terminal
what happens when histamine is exposed to diamine oxidase and what happens when that product is exposed to ribose
gets converted into imidazoleacetic acid
converted into imidazoleacetic acid riboside
what converts N-methylhistamine into N-methylimidazole acetic acid
MAO-B
storage of histamine in the lung, skin, gut and stomach
lung - 15μg/g of tissue
skin - 6-8μg/g
gut - 60-80μg/g
stomach - 10μg/g
what do mast cell granules contain
histamine bound to a proteoglycan core - usually heparin
also contains proteolytic enzymes:
- tryptase
- chymase
what happens when activation of mast cells occur
granules fuse with the membrane, releasing histamine
what is IgE
a receptor on the surface of mast cells
what causes allergic reactions
IgE exposed to allergen
causes release of granules and histamine
IgE dependent release of histamine
what can mast cells also be activated by
bacterial products - lipopolysaccharide
complement peptides - C3a and C5a
name 2 drugs that release histamine by non-receptor action and another non-specific reason histamine is released
morphine
tubocurarine
trauma to tissues
features of H1
wide distribution in cardiovascular system, smooth muscle and nerves
features of H2
regulates gastric acid secretion in the stomach
increases HR and CO
actions of H1
vasodilation
increased vascular permeability
stimulation of peripheral nerves
smooth muscle contractions
what is the action of histamine on cardiovascular system
constricts arteries and veins
dilates arterioles and capillaries
what can a large dose of histamine cause
a large drop in blood pressure and fluid loss in the capillaries
leads to circulatory collapse - anaphylactic shock
(severe allergic reaction)
what are H1 antagonists and the difference
mepyramine
cetirizine - causes less problems with drowsiness, impermeable to BBB
actions of H1
stimulate gastric acid secretion
regulates cardiac output and rate
modulates actions of immune cells
how is gastric acid synthesis blocked
histamine binding to H2R receptor of parietal cell
what is a classical H2 antagonist
cimetidine
function of cimetidine
inhibits cytochrome P450
actions of H3
can act as a neurotransmitter
actions of H4
appear on inflammatory cells
appear to regulate cytokine network in the inflammatory response
what is 5-hydroxytryptamine known as
seretonin
where is 5-HT found
CNS
GI tract
in platelets
outline the synthesis of 5-HT
tryptophan hydroxylase converts tryptophan into 5-hydroxytryptophan
L-aromatic acid decarboxylase converts it into 5-HT
why does dietary intake of 5-HT not contribute to the body’s pool of 5-HT
it is rapidly metabolised and excreted in the urine
outline the metabolism of 5-HT
monoamine oxidase (MAO) converts 5-HT into an intermediary with an aldehyde
aldehyde dehydrogenase converts it into 5-hydroxyindole acetic acid (5-HIAA)
where is 5-HT synthesised
in the CNS and enterochromaffin cells in the gut
where is 90% of 5-HT stored
in the gut
what type of receptor is 5-HT3
internal cationic channel
what are the transducers instead of cAMP of 5-HT2a/b/c
IP3/DAG
where are 5-HT1 receptors located
mainly in the CNS
role of 5-HT1 recptors
mood/behaviour
thermoregulation
feeding
sleep
what can activation of 5-HT1 cause
neural inhibition
vasoconstriction
what is the most effective 5-HT1 agonist
sumatriptan
5-HT1D agonist
what 5-HT1 antagonist works on all 5-HT1 receptor subtypes
methiothepin
where are 5-HT2 receptors located
in the CNS
widely distributed in the periphery
how does LSD effect 5-HT2 receptors
agonist at central receptors - causing hallucination
antagonist of receptors in the periphery
what are the antagonists for 5-HT2
methysergide
ketotifen
function of 5-HT3 found in the brain and the periphery
periphery - evokes pain
brain - involved in vomiting reflex
what is a 5-HT3 antagonist and its use
ondansetron - anti-emetics
controls severe vomiting and nausea after chemotherapy
where is 5-HT4 located and its function
found in the CNS
regulates gut motility
5-HT4 antagonist and its use
tegaserod
used to treat abdominal discomfort, bloating constipation and chronic idiopathic constipation
5-HT in relation to migraines and what is found in the urine of those with migraines
5-HT causes vasoconstriction in the cerebral arteries
5-HIAA
5-HT in relation to migraines and what is found in the urine of those with migraines
5-HT causes vasoconstriction in the cerebral arteries
5-HIAA
how is GI motility stimulated
directly - 5-HT2 receptors on smooth muscle cell
indirectly - 5-HT3/4 receptors on enteric neurons
what happens when 5-HT receptors are stimulated in the stomach
fluid secretion
nausea
vomiting
