Flashcards in Serotonin/histamine basic science Deck (21):
What are the four places where in the body where serotonin is found?
1. enterochromaffin cells of the GI tract
2. Platelets (taken up from the blood)
3. CNS (mostly localized to the Raphe nuclei)
What is the role of serotonin in the enterochromaffinc cells of the GI tract?
regulate intestinal motility and may play a role in mediating emesis. Most circulating serotonin (5HT) derived from these cells)
What is the role of serotonin in the platelets?
play a role in blood clotting by causing local vasoconstriction. Also promotes platelet aggregation. Platelets take up serotonin and store it in granules.
What is the role of serotonin in the CNS?
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.
Synthesis of serotonin: Starting material, rate limiting enzyme. What enzyme does it share with dopamine synthesis?
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)
What is the major mechanism for inactivation of synaptic 5-HT?
reuptake by serotonin reuptake pumps similar to, but distinct from, NET and DAT.
What is fluoxetine?
selective seratonin reuptake inhibitor (SSRI)
prevents reuptake of serotonin
What enzyme is used to degrade serotonin? One product of serotonin degradation?
MAO. serotonin is a precursor to melatonin in the pineal gland.
What do 5-HT-1 receptors do,biochemically? What are their effects on the body?
linked negatively to adenylyl cyclase.
prevent neurotransmitter release presynamptically.
Target of triptans (sumatriptan- this acts as an agonist) to treat migraines.
What do 5HT2 receptors do, and whas is their effect on tissues?
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.
What do 5HT3 receptors do, and what is their effect on target organs?
ligand gated ion channel (these are the exceptions). Cause depol of afferent nerves. In the stomach, this causes emesis
Where is histamine important (cells)? Include where histamine comes from, and also cells that use it as a signaling molecule.
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.
Describe the synthesis of histamine: starting chemical, important emzymes, storage.
derived from histidine
catalyzed by histidine decarboxylase (most of the time) or by AADC. this is a decarboxylation rxn.
stored in granules
How is histamine inactivated?
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
What happens when histamine binds an H1 receptor? Biochemistry and body effects
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)
What happens when histamine binds an H2 receptor? Biochemsitry and body effects
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.
What should I know about histamine H3 and H4 receptors?
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.
What is the triple response of Lewis?
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.
What are the 3 most important effects of histamine release from mast cells?
1. vasodilation- should be local
3. increased capillary permeability- edema formation.
How does histamine release trigger gastric acid secretion?
released from enterochromaffin-like cells
acts on H2 receptors on parietal cells
activates the proton pump