Histamine and Serotonin Lecture Flashcards
What AA is histamine synthesized from?
Histidine
Describe the release and storage of histamine?
It is released as it is made, large amounts dont tend to build up
What histamine degradation product can be measured in the urine?
N-methylimidazole acetic acid
Where are the largest concentrations of histamine found? (areas of body)
Skin, lungs, GI and nasal mucosa, and blood
so sites that are potential for tissue injury
What two cells principally produce and store histamine?
Mast cells and basophils
What mediates histamine release form mast cells?
Calcium
What type of G-proteins are the H1 and H2 receptors coupled to? and where are they distributed?
H1 - Gq - smooth muscle, endothelium, brain
H2 - Gs - Gastric mucosa, cardiac muscle, mast cells, brain
What are the principle physiological effects of histamine on the cardiovascular system?
- 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)
What effect does histamine have on bronchiolar smooth muscle, which receptor mediates this?
Bronchoconstriction (H1)
What effects does histamine have on the GI tract?
- contraction of intestinal smooth muscle; diarrhea (H1)
- Stimulates gastric acid, pepsin, and intrinsic factor secretion (H2 receptors)
What effect does histamine have on the nervous system?
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
What is a physiological antagonist to histamine that has opposite effects on smooth muscle through different receptors?
Epinephrine
What are some general side effects from antihistamine H1 antagonist drugs?
Sedation and atropine like effects
What product in the urine can be used to measure serotonin levels?
5-hydroxyindolacetic acid (5-HIAA)
What amino acid is serotonin made from? What is the rate limiting enzyme
Tryptophan
Tryptophan hydroxylase
Describe the distribution of Serotonin in the body?
GI - tract 90%
platelets - 8%
CNS - 2% raphe nuclei of brain stem
What are the effects of serotonin on the GI tract?
Contraction of smooth muscle (increase tone and facilitate peristalisis)
Carcinoid syndrome
What are the effects of serotonin on the cardiovascular system?
1 powerful vasoconstrictor in smooth muscle; vasodilator in skeletal muscle.
2 Activation of chemoreceptor nerve endings to cause reflex bradycardia
3 platelet aggregation
What are the effects of serotonin on the PNS and CNS?
CNS- mood, food intake, sleep, pituitary secretions
PNS - Stimulate nociceptive sensory nerve endings
also have autoreceptor actions
In general what receptors do ergot alkaloids function on?
both classes have both agonist and antagonist actions at serotonin and alpha adrenergic and some dopamine receptor
What effects do ergot alkaloids have on the CNS, vascular smooth muscel, and uterine smooth muscle
CNS - powerful hallucinogens
Vascular Smooth Muscle - blood vessel constriction
Uterine smooth muscle - prolonged contractions at high dose
