Serotonin Flashcards
Describe the synthesis of Serotonin
- From essential amino acid tryptophan
- Tryptophan hydroxylase is the RLS. Tyrptophan concentration is what limits synthesis in the brain
- L-aromatic amino acid decarboxylase -similar enzyme used for catecholamine synthesis
What happens to serotonin in the pineal gland
converted to melatonin
What is Serotonin metabolized to and by what
Metabolized to 5-hydroxyindole acetic acid by monoamine oxidase
-neuronal action terminated primarily by a high affinity active uptake system (SERT) and then intraneuronal conversion to 5-hydroxyindoleacetic acid
Where is the majority of serotonin located
- GI system-90%
- Platelets-8% (not synthesized here)
- CNS-2%
* cell bodies in midbrain raphe nucleus that project to
- hypothalamus neostriatum, limbic forebrain, neocortex, medulla, spinal cord
Describe the serotonin receptors
- there are 13 receptor subtypes! Most are G-protein coupled. there are neuronal autoreceptors
- the receptor that is not G-protein coupled is 5-HT3 which is a ligand-gated Cation channel
- 5HT 1(A-E) inhibition of adenylate cyclase. 5-HT1A also opens K channels
- 5-HT2(A-C) : PI hydrolysis
- 5HT4-7: activation of adenylate cyclase or unknown
- auto-receptors decrease serotonin release-1A like also 1D
Serotonin in the GI system
-synthesis and storage; both neuronal and non-neuronal slow turnover-1 day
- contracts GI smooth muscle including esophagus, stomach and intestine-increasing tone, peristalsis and diarrhea
- Emesis -5-HT3 receptors in GI tract and brain
- Carcinoid syndrome-tumors of enterochromaffin cells (enterochromaffin cells are what make serotonin in the GI system)
Carcinoid syndrome
- tumors of enterochromaffin cells.
- Secrete serotonin and bradykinin
- They can cause severe diarrhea and asthma
- Treatment: somatostatin analogs (octreotide) which blocks the secretion of all mediators from the carcinoid tumor or serotonin antagonists
Serotonin and the Cardiovascular system
- potent vasoconstriction of large arteries and veins;cranial (5HT1D) blood vessels
- vasodilation in coronary, skeletal muscle and cutaneous blood vessles
- Bezold-Jarisch refelx-coronary chemoreceptors
- bradycardia, hypotension and hypoventilation
-platelet aggregation-active uptake of serotonin from circulation
Serotonin as a neurotransmitter
- cell bodies n midbrain raphe nuclei Project both rostrally and caudally
- May be involved in:
- sensory perception-LSD
- Sleep-slow wave deep sleep
- Temperature regulation
- Neuroendocrine regulation-release of ACTH, GH, prolactin, TSH, FSH, and LH
- learning and memory, particularly short-term memory
Other things Serotonin does in the CNS
- Pain perception: spinal and brain sites of action
- Drug abuse
- Emesis-5HT3 receptors
- Mental Illness
Serotonin and mental illness
- Affective disorders-SSRIs and SNRIs
- Schizophrenia-atypical antipsychotics
- Obsessive compulsive disorder-SSRIs
- Anxiety-5HT1A receptors
Serotonin Agonists
Lysergic acid diethylamide
-relatively nonspecific 5HT2 receptors. Potent hallucinogen
- Buspirone.
- Sumatriptan
Buspirone
-5HT1A receptor partial agonist-Antianxiety
Sumatriptan
- 5-HT 1D and 1B receptors on cerebral blood vessels
- inhibit release of vasoactive peptides-Calcitonin gene related peptide (CGRP)
- promote vasoconstriction
- treatment of migraine headaches. stop existing ones
- side effects include nausea, vomiting, angina, dizziness and flushing
Lorcaserin
Diet drug
-for obese adults (BMI over 30) or BMI of 27 or greater with one other weight related health condition
-selective 5-HT2C receptor agonist. the activation of this 5-HT2C receptor in the hypothalamus is supposed to activate POMC (Proopiomelanocortin) production and consequently promote weight loss through satiety
