Histamine and Serotonin Lecture

Question 1

What AA is histamine synthesized from?

Answer 1

Histidine

Question 2

Describe the release and storage of histamine?

Answer 2

It is released as it is made, large amounts dont tend to build up

Question 3

What histamine degradation product can be measured in the urine?

Answer 3

N-methylimidazole acetic acid

Question 4

Where are the largest concentrations of histamine found? (areas of body)

Answer 4

Skin, lungs, GI and nasal mucosa, and blood

so sites that are potential for tissue injury

Question 5

What two cells principally produce and store histamine?

Answer 5

Mast cells and basophils

Question 6

What mediates histamine release form mast cells?

Answer 6

Calcium

Question 7

What type of G-proteins are the H1 and H2 receptors coupled to? and where are they distributed?

Answer 7

H1 - Gq - smooth muscle, endothelium, brain

H2 - Gs - Gastric mucosa, cardiac muscle, mast cells, brain

Question 8

What are the principle physiological effects of histamine on the cardiovascular system?

Answer 8

• Immediate fall in blood pressure due to peripheral vasodilation (H1 and H2)
• increase in vascular permeability causing edema and loss of plasma from circulation (H1)
• Increased contractility and heart rate (H2…minor effect in humans)

Question 9

What effect does histamine have on bronchiolar smooth muscle, which receptor mediates this?

Answer 9

Bronchoconstriction (H1)

Question 10

What effects does histamine have on the GI tract?

Answer 10

• contraction of intestinal smooth muscle; diarrhea (H1)

- Stimulates gastric acid, pepsin, and intrinsic factor secretion (H2 receptors)

Question 11

What effect does histamine have on the nervous system?

Answer 11

Stimulant of sensory nerve endings: Pain (dermis) and itching (epidermis) (H1)
H3 receptors function as autoreceptors in the CNS and histamine fn as a neurotransmitter

Question 12

What is a physiological antagonist to histamine that has opposite effects on smooth muscle through different receptors?

Answer 12

Epinephrine

Question 13

What are some general side effects from antihistamine H1 antagonist drugs?

Answer 13

Sedation and atropine like effects

Question 14

What product in the urine can be used to measure serotonin levels?

Answer 14

5-hydroxyindolacetic acid (5-HIAA)

Question 15

What amino acid is serotonin made from? What is the rate limiting enzyme

Answer 15

Tryptophan

Tryptophan hydroxylase

Question 16

Describe the distribution of Serotonin in the body?

Answer 16

GI - tract 90%
platelets - 8%
CNS - 2% raphe nuclei of brain stem

Question 17

What are the effects of serotonin on the GI tract?

Answer 17

Contraction of smooth muscle (increase tone and facilitate peristalisis)
Carcinoid syndrome

Question 18

What are the effects of serotonin on the cardiovascular system?

Answer 18

1 powerful vasoconstrictor in smooth muscle; vasodilator in skeletal muscle.
2 Activation of chemoreceptor nerve endings to cause reflex bradycardia
3 platelet aggregation

Question 19

What are the effects of serotonin on the PNS and CNS?

Answer 19

CNS- mood, food intake, sleep, pituitary secretions
PNS - Stimulate nociceptive sensory nerve endings

also have autoreceptor actions

Question 20

In general what receptors do ergot alkaloids function on?

Answer 20

both classes have both agonist and antagonist actions at serotonin and alpha adrenergic and some dopamine receptor

Question 21

What effects do ergot alkaloids have on the CNS, vascular smooth muscel, and uterine smooth muscle

Answer 21

CNS - powerful hallucinogens
Vascular Smooth Muscle - blood vessel constriction
Uterine smooth muscle - prolonged contractions at high dose