Histamine and Serotonin

Question 1

Serotonin other name

Answer 1

5-H (5-Hydroxytryptamine)

Question 2

How does histamine cause effect

Answer 2

Via H1,2,3&4 rec
Subtypes account for effect variability
H2 is responsible for controlling gastric acid secretion

Question 3

Histamine effects

Answer 3

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

Question 4

Histamine distribution

Answer 4

Widely distributed
(High level goats and rabbits
Lower level cats dogs humans horses)

Question 5

Histamine production pathway

Answer 5

Histidine - histamine by action of L-histidine decarboxylase enz

Question 6

Histamine production sites

Answer 6

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

Question 7

Histamine storage

Answer 7

Mast cells (main)
Basophil in the blood
High histamine con in skin and intestinal and bronchial mucosa due to high mast cell level

Question 8

Histamine release in carnivores cause

Answer 8

Hypotension

Question 9

Histamine release in rabbits cause

Answer 9

Bronchoconstriction and R heart dilation

Question 10

Histamine release in guinea pigs cause

Answer 10

Bronchiconstriction and asphyxiation

Question 11

Anaphylaxis and allergy histamine release pathway

Answer 11

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

Question 12

Drugs and chemicals that can cause direct mast cell degran and hist release

Answer 12

Morphine
Codeine
Pp antibiotics
Neuromuscular blocking agents
(Also endogenous molecules like bradykinin)

Question 13

Effect of physical injury eg scratch to skin surface

Answer 13

Redness and urtication due to histamine release locally

Triple response of redness, swelling, flare

Question 14

CV syst effects of Hist

Answer 14

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)

Question 15

Resp system effects of hist

Answer 15

Bronchoconstriction (esp GP)
Bronchial relaxation (sheep H2)
Tracheal relaxation (cats)

Question 16

Intestinal smooth muscle effects of histamine

Answer 16

Gen contracted

Question 17

Uterine smooth muscle effect of histamine

Answer 17

Gen contracted

Question 18

Exocrine gland effects of histamine

Answer 18

Gastric acid secretion incr mediated by H2

Question 19

H1 rec pathway sognalling

Answer 19

GPCR

Coupled to PLC which converts PiP2 to DAG and IP3 which incr IC Ca 2+ levels

Question 20

H2 rec pathway signallinc

Answer 20

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

Question 21

Incr cA and GMP levels promote

Answer 21

Vascular relaxation

Question 22

2nd messenger from rec dep on

Answer 22

Cell type
Rec type
Alpha subunit type that will act when bound to GTP and then convert it to GDP

Question 23

How hist cause incr vasc permeability

Answer 23

Phosphorylate IC adhesion molecule cadherin causes gaps between endo cells to appear

Question 24

Hist effects of leucocytes

Answer 24

Can trigger cytokine release and other inflamm mediators

Question 25

Hist Effect on chronic inflamm

Answer 25

Affect macroph B and T lymphocyte fx, cytokine prod, MHC c2 antigens expression on cell surface

Question 26

H1 antihistamines

Answer 26

Block H1 rec Distinct from physiological antagonism Well absorbed after oral administration by monogastrics, not ruminants More pronounced side effects with IV administration

Question 27

Antihistamine effects

Answer 27

Counteract effects of allergic reactions and anaphylactic type reactions

Question 28

Specific antihistamines

Answer 28

``` Diphenhydramine Cyproheptadine Chlorphenamine Levobastine Iodoxamine ```

Question 29

Specific a-h uses

Answer 29

Cns effects (travel anxiety) Allergy conjunctivitis Feline asthma Skin? (Eg excessive grooming in cats)

Question 30

Serotonin synth

Answer 30

Trytophan (in diet) to 5-hydroxytryptophan to 5-hydroxytrptamind

Question 31

Serotonin metabolism

Answer 31

5-hydroxytryptamine to 5-HIAA catabolised by MAO

Question 32

Receptor subgroups and structures

Answer 32

5HT1,2,3,4 | Most GPCR only 3 is ion gated

Question 33

Role in inflam

Answer 33

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?

Question 34

5HT1 agonist

Answer 34

Sumatriptan | Used in migraine management

Question 35

5HT3 antagonist

Answer 35

Ondansetron | Used in management of chemo induced emesis

Question 36

SSRIs

Answer 36

Serotonin reuptake inhibitors | Used in depression management eg fluoxetine and sertraline

Question 37

GIT relation to 5HT

Answer 37

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

Question 38

Platelet relation to 5HT

Answer 38

Store but dont synth | Release promotes platelet aggregation and local vasoconstriction

Question 39

CNS relation to 5HT

Answer 39

Multiple effects, affects wake/sleep cycle, behaviour, anxiety