Histamine and Serotonin Flashcards
Serotonin other name
5-H (5-Hydroxytryptamine)
How does histamine cause effect
Via H1,2,3&4 rec
Subtypes account for effect variability
H2 is responsible for controlling gastric acid secretion
Histamine effects
Smooth m contraction of bronchi, gut and large vessels
Smooth m relaxation of small arterioles - cause drop in BP
Incr vasc perm (immediate)
Incr gastric acid secretion
Histamine distribution
Widely distributed (High level goats and rabbits Lower level cats dogs humans horses)
Histamine production pathway
Histidine - histamine by action of L-histidine decarboxylase enz
Histamine production sites
Mast cell has slow synthesis then stores due to slow turnover depletion can occur
Faster synth rate at gastric mucosa parietal cells
CNS neurons and lymphocytes also synth it
Histamine storage
Mast cells (main) Basophil in the blood High histamine con in skin and intestinal and bronchial mucosa due to high mast cell level
Histamine release in carnivores cause
Hypotension
Histamine release in rabbits cause
Bronchoconstriction and R heart dilation
Histamine release in guinea pigs cause
Bronchiconstriction and asphyxiation
Anaphylaxis and allergy histamine release pathway
Antigen-IgE interaction on mast cell surface
Cause incr IC Ca2+ level (effect TFs and trigger cytokine release)
Complex histamine released
Histamine released from storage granules
Drugs and chemicals that can cause direct mast cell degran and hist release
Morphine Codeine Pp antibiotics Neuromuscular blocking agents (Also endogenous molecules like bradykinin)
Effect of physical injury eg scratch to skin surface
Redness and urtication due to histamine release locally
Triple response of redness, swelling, flare
CV syst effects of Hist
Originally H1 assoc but at high dose also H2
Constrict large vessels generally, and dilate arterioles and microcirc
Species variation as to dom (eg rabbit pressor effect dom, carnivore vasodil of microcirc dom)
Resp system effects of hist
Bronchoconstriction (esp GP) Bronchial relaxation (sheep H2) Tracheal relaxation (cats)
Intestinal smooth muscle effects of histamine
Gen contracted
Uterine smooth muscle effect of histamine
Gen contracted
Exocrine gland effects of histamine
Gastric acid secretion incr mediated by H2
H1 rec pathway sognalling
GPCR
Coupled to PLC which converts PiP2 to DAG and IP3 which incr IC Ca 2+ levels
H2 rec pathway signallinc
GPCR
Linked to adenylyl cyclase act which converts ATP to cAMP so incr cAMP level which act on Pro Kinase A which opens ca2+ chamnels
Incr cA and GMP levels promote
Vascular relaxation
2nd messenger from rec dep on
Cell type
Rec type
Alpha subunit type that will act when bound to GTP and then convert it to GDP
How hist cause incr vasc permeability
Phosphorylate IC adhesion molecule cadherin causes gaps between endo cells to appear
Hist effects of leucocytes
Can trigger cytokine release and other inflamm mediators
Hist Effect on chronic inflamm
Affect macroph B and T lymphocyte fx, cytokine prod, MHC c2 antigens expression on cell surface
H1 antihistamines
Block H1 rec
Distinct from physiological antagonism
Well absorbed after oral administration by monogastrics, not ruminants
More pronounced side effects with IV administration
Antihistamine effects
Counteract effects of allergic reactions and anaphylactic type reactions
Specific antihistamines
Diphenhydramine Cyproheptadine Chlorphenamine Levobastine Iodoxamine
Specific a-h uses
Cns effects (travel anxiety)
Allergy conjunctivitis
Feline asthma
Skin? (Eg excessive grooming in cats)
Serotonin synth
Trytophan (in diet) to 5-hydroxytryptophan to 5-hydroxytrptamind
Serotonin metabolism
5-hydroxytryptamine to 5-HIAA catabolised by MAO
Receptor subgroups and structures
5HT1,2,3,4
Most GPCR only 3 is ion gated
Role in inflam
Incr platelet aggregation and vasc permeab
Play role in autoimm disease eg RA
Incr COX-2 level which incr inflam mediator production
May be mediated by spec sub types of rec?
5HT1 agonist
Sumatriptan
Used in migraine management
5HT3 antagonist
Ondansetron
Used in management of chemo induced emesis
SSRIs
Serotonin reuptake inhibitors
Used in depression management eg fluoxetine and sertraline
GIT relation to 5HT
Produces and stores 5HT locally in enterochromaffin cells (main source)
Helps control GI fx
Can be excitatory or inhibitory dep on location and sub type
Platelet relation to 5HT
Store but dont synth
Release promotes platelet aggregation and local vasoconstriction
CNS relation to 5HT
Multiple effects, affects wake/sleep cycle, behaviour, anxiety
