Neurochemistry 3 Flashcards
What are biogenic amines implicated in
e.g. movement, reward, addiction, depression, sleep
Name 5 biogenic amines
Dopamine (catecholamine)
Norepinephrine (catecholamine)
Epinephrine (catecholamine)
Indoleamine - serotonin (5-HT)
Imidazoleamine - histamine
Name 3 catecholamines
Dopamine
Norepinephrine
Epinephrine
Synonym for serotonin
Where is it present
What is it synthesised from
What are high AND low serotonin levels associated with
what drugs use serotonergic neurons as their target
5-HT - 5-hydroxytryptamine
Present in serum (initially thought to increase vascular tone)
Synthesised from tryptophan
High serotonin - happiness, sleep, appetite, sex drive
low serotonin - depression & anxiety
Certain antipsychotic drugs in treatment of depression and anxiety act specifically on serotonergic neurons
Rate limiting step in synthesis of serotonin
Tryptophan hydroxylase
Describe the serotonin receptors
Most are GPCRs linked to G proteins that modulate cAMP production and phospholipase C activity
5-HT3 receptor is a ligand gated Na+ channel
(5-HT 1-7)
2 classes of serotonin reuptake inhibitors
TCAs - tricyclic anti-depressants - inhibit reuptake of serotonin and norepinephrine
SSRIs - selective serotonin reuptake inhibitors - e.g. fluoxetine (prozac)
What does tyrosine hydroxylase do
Where is it found
How is its expression controlled
Controls rate limiting step
Only found in symapthetic neurons and adrenal chromaffin cells
Diagnostic of a chatecholaminergic cell
Its expression in a cell is controlled by Nerve Growth Factor and other factors controlling growth and differentiation of sympathetic neurons
What structures have a common origin in early embryonic development
SNS and adrenal gland
Synthesis of catecholamines
How are NTs (catecholamines & indoleamines) taken into and stored in vesicles
Vesicular Monoamine Transporter (VMAT)
Can transport catecholamines and indoleamines
What is VMAT inhibited by
Reserpine
Used before to treat hypertension and psychosis
Mediates its actions by depleting dopamine in nerve terminal - inhibits all catecholamine so not specific
What do vesicles in adrenergic neurons and chromaffin cells contain
Dopamine B-hydroxylase (DBH)
Name of vesicles in adrenal chromaffin cells
Chromaffin granules
Where is norepinephrine synthesised
Within the synaptic vesicles - THE ONLY 1
Hence, as adrenal chromaffin cells = chromaffin granules, epinephrine is produced in the chromaffin granules
What type are catecholamine receptors
All are coupled to G proteins
What receptors does dopamine bind to
D1-5
What are the D1-like receptors
MOA
D1 & D5
Activate adenylate cyclase - increases cAMP
What are the D2-like receptors
MOA
Inhibit adenylate cyclase - decreases cAMP
3 mechanisms of inactivation of biogenic amines
- reuptake via dopamine transporter - Na+ dependent transport protein which is INHIBITED BY cocaine & amphetamine
- Enzymatic degradation
- Diffusion away from synaptic cleft
MOA of cocaine and amphetamine
Inhibit reuptake via dopamine transporter (Na+ dependent)
What is the enzymatic inactivation of dopamine
Function of monamine oxidase
What is it associated with
What does it work with
MAO enzymes deaminate catecholamines → inactive derivatives
Associated with outer mito. membrane
Works with AD - aldehyde dehydrogenase
MOA of COMT - catechol-O-methyltransferase
Where is it found
Transfers methyl groups to hydroxyl group of catechols
Cytosolic
What diseases is the dopamine system associated with
Parkinsons
Attention deficit hyperactivity disorder
Tourette syndrome
Schizophrenia
Bipolar disorder
Addiction
Pathophysiology of Parkinsons
Insufficient dopamine in the nigrostriatal pathway
Dopaminergic neurons project from the substantia nigra to the striatum
Neural projections in motor control
What happens to our dopamine producing cells as we age
How does this change in Parkinsons
Form neuromelanin
What are the familial mitochondrial alterations in Park genes
Mitochondrial dysfunction - Parkin (Park2), DJ-1 (Park7), PINK (Park6)
Familial alterations in Park genes - UPS
Defects in ubiquitin-proteasome system (UPS)
Alpha-synuclein (Park1)
Parkin
DJ-1
Sporadic causes of Parkinsons
Environmental toxins - MPTP, rotenone
Oxidation of dopamine - 6-hydroxydopamine
What does the biochem of parkinsons cause in the cell
Oxidative stress
Protein aggregation
What is the main component of lewy bodies
How do they change with Parkinsons
Synupian
Sites of action of common treatments for Parkinsons
Levodopa
Increases dopamine levels
Selegeline
Inhibits MAO-B
Amantidine
Stimulates release of DA
Inhibits reuptake
DA Agonists
Bind to DA receptors
COMT inhibitors
Block degradation of DA and L-DOPA
