Inflammation-Histamine and Serotonin

Question 1

What receptors cause histamine effects? What are the effects of histamine?

Answer 1

H1, H2, H3, and H4 receptors

smooth muscle contraction of bronchi, gut, and vessels
smooth muscle relaxation of small arterioles (fall in BP)
increased vascular permeability
increased secretion of gastric acid

Question 2

Where is histamine stored?

Answer 2

Mast cell: slow synthesis
Basophil in blood

CNS neurons, gastric mucosa parietal cells, and lymphocytes also produce it

Question 3

What are the effects of histamine release in various species?

Answer 3

Carnivores: hypotension
Rabbits: bronchoconstriction and right heart dilation
Guinea pigs: bronchoconstriction and asphyxiation

Question 4

What happens when histamine is released from storage granules?

Answer 4

Anaphylaxis

• antigen reacts with IgE on mast cell surface
• increase in intracellular Ca
• release of histamine

Question 5

Histamine effects on systems

Answer 5

Cardio: generally constriction of large vessels and dilation of arterioles and microcirculation; species variation

Respiratory: bronchoconstriction; tracheal relaxation in cats; bronchial relaxation in sheep

Intestinal: smooth muscle contraction

Uterine: smooth muscle contraction (except rat)

Exocrine glands: gastric acid secretion

increased vascular permeability

triggers release of cytokines and other inflammatory mediators

Question 6

What are the effects of H1 and H2 receptor activation?

Answer 6

H1: increased intracellular calcium

H2: increased cAMP

Question 7

What receptors do anti-histamines work on and how do they work?

Answer 7

H1 receptor antagonists

• physically block Hi receptor, preventing access to histamine
• well absorbed after oral admin (not in ruminants)
• counter the effects of allergic type reactions and certain responses to anaphylactic type reactions

Have no effect on H2 receptor mediated effects (gastric acid secretion, some vascular effects)

Question 8

Where is serotonin (5-hydroxytryptamine, 5-HT) concentrated?

Answer 8

enterochromaffin cells in GI tract
platelets
CNS

Question 9

What is serotonin synthesized from? What catabolizes its breakdown?

Answer 9

tryptophan

Monoamine oxidase (MAO)

Question 10

What are the effects of serotonin?

Answer 10

Platelets: store but don’t synth it, release promotes aggregation and local vasoconstriction, increased vascular permeability

GI: control GI function, excitatory or inhibitory (depends on location and subtype of receptor)

CNS: affects sleep/wake cycle, behavior, anxiety, etc

Question 11

What drugs effect serotonin production?

Answer 11

Sumatriptan: agonistic, management of migraines

Ondansetron: antagonistic, manage chemo-induced emesis

Fluoxetine, sertraline: reuptake inhibitors, manage depression