Serotonin/histamine basic science

Question 1

What are the four places where in the body where serotonin is found?

Answer 1

1. enterochromaffin cells of the GI tract
2. Platelets (taken up from the blood)
3. CNS (mostly localized to the Raphe nuclei)
4. hypothalamus

Question 2

What is the role of serotonin in the enterochromaffinc cells of the GI tract?

Answer 2

regulate intestinal motility and may play a role in mediating emesis. Most circulating serotonin (5HT) derived from these cells)

Question 3

What is the role of serotonin in the platelets?

Answer 3

play a role in blood clotting by causing local vasoconstriction. Also promotes platelet aggregation. Platelets take up serotonin and store it in granules.

Question 4

What is the role of serotonin in the CNS?

Answer 4

sleep, mood, migraines, hallucinations, sexual activity, aggression. drugs that increase serotonin tend to increase mood and self confidence.

in the hypothalamus, serotonin helps control body temp and release of pituitary hormones.

Question 5

Synthesis of serotonin: Starting material, rate limiting enzyme. What enzyme does it share with dopamine synthesis?

Answer 5

start with tryptophan
tryptophan hydroxylase is the rate-limiting enzyme- similar to tyrosine hydroxylase for the synthesis of dopamine.
AADC shared with dopamine synthesis (aromatic amino acid decarboxylase)

Question 6

What is the major mechanism for inactivation of synaptic 5-HT?

Answer 6

reuptake by serotonin reuptake pumps similar to, but distinct from, NET and DAT.

Question 7

What is fluoxetine?

Answer 7

aka prozac
selective seratonin reuptake inhibitor (SSRI)
prevents reuptake of serotonin

Question 8

What enzyme is used to degrade serotonin? One product of serotonin degradation?

Answer 8

MAO. serotonin is a precursor to melatonin in the pineal gland.

Question 9

What do 5-HT-1 receptors do,biochemically? What are their effects on the body?

Answer 9

linked negatively to adenylyl cyclase.
prevent neurotransmitter release presynamptically.
Target of triptans (sumatriptan- this acts as an agonist) to treat migraines.

Question 10

What do 5HT2 receptors do, and whas is their effect on tissues?

Answer 10

linked positively to phospholipase C and increase PKC and Ca levels
Yield vasodilation in some vascular beds by stimulating NO release of endothelial cells. Yield vasoconstriction in other beds by incr. Ca stores in vascular smooth muscle.
increase blood clotting.

Question 11

What do 5HT3 receptors do, and what is their effect on target organs?

Answer 11

ligand gated ion channel (these are the exceptions). Cause depol of afferent nerves. In the stomach, this causes emesis

Question 12

Where is histamine important (cells)? Include where histamine comes from, and also cells that use it as a signaling molecule.

Answer 12

1. Mast cells: predominant storage site. Mast cells especially seen in the skin, bronchial mucosa, intestinal mucosa.
2. gastric mucosal cells- stimulate gastric acid secretion from stomach parietal cells. (freleased from enterochromaffin-like cells)
3. CNS neurons: acts as a neurotransmitter.

Question 13

Describe the synthesis of histamine: starting chemical, important emzymes, storage.

Answer 13

derived from histidine
catalyzed by histidine decarboxylase (most of the time) or by AADC. this is a decarboxylation rxn.
stored in granules

Question 14

How is histamine inactivated?

Answer 14

generally inactivated by degradation.

1. Histamine N-methyltransferase, which is the major mechanism and is a widely distributed enzyme.
2. MAO or other similar enzyme

Question 15

What happens when histamine binds an H1 receptor? Biochemistry and body effects

Answer 15

positive link to phospholipase C: incr. intracellular Ca and activation of NO.
causes vasodilation in the blood vessels (NO/cGMP pathways), increased capillary permeability (localized inflammation), bronchoconstriction (less important in humans), sensory nerve afferent excitation (itch and pain; increased vasodilation)

Question 16

What happens when histamine binds an H2 receptor? Biochemsitry and body effects

Answer 16

positive link to adenylyl cyclase
increased gastric secretion by parietal cells in the stomach
vasodilation of blood vessels that is slower in onset but longer in duration than vasodilation mediated solely by H1 receptors.

Question 17

What should I know about histamine H3 and H4 receptors?

Answer 17

both are linked negatively to adenylate cyclase
H3 found in the CNS and inhibit the release of histamine from nerve terminals
H4 found in cells of hematopoietic origin.

Question 18

What is the triple response of Lewis?

Answer 18

seen after indradermal histamine response.

1. localized red spot: due to direct vasodilaing effects of H1 activation
2. flare: slower develping rxn around the localized red spot from effects on both H2 and H1.
3. wheal: white area at injection site that is due to H1 induced capillary permeability.

Question 19

What are the 3 most important effects of histamine release from mast cells?

Answer 19

1. vasodilation- should be local
2. bronchoconstriction
3. increased capillary permeability- edema formation.

Question 20

How does histamine release trigger gastric acid secretion?

Answer 20

released from enterochromaffin-like cells
acts on H2 receptors on parietal cells
generates cAMP
activates PKA
activates the proton pump

Question 21

What is the role of histamine in the CNS?

Answer 21

most important fact to know: histamine increases wakefulness via H1 receptors in humans