Catecholamines and 5HT- Salmen Flashcards
which neurotransmitters are catecholamines (CA)? what is the difference between serotonin and other CAs?
- Dopamine
- Norepinephrine
- Epinephrine
- Serotonin- is an indolamin and derives from the amino acid tryptophan
where is dopamine produced? what are the 3 projection pathways of dopamine?
dopamine is produced in 3 locations:
- Substantia nigra
- Ventral tagmental area (VTA)
- Hypothalamus
Each production site projects to other areas in the brain:
- from substantiated nigra–> to the dorsal striatum
- from VTA–> ventral striatum, amygdala, hippocampus, cortex (PFC, cingulate)
- Hypothalamus–>anterior pituitary
in which brain regions would you find the highest density of different types of dopamine receptors?
- D1-D5 - cortex and limbic system, basal ganglia (very dense with all DA receptors)
- D1 + D2- corpus striatum
- D3 + D5- hypothalamus
- D4- basal ganglia and limbic system
Where is norepinephrine produced?
- 50% of NE is produced in the locus ceruleus (main NE supplier)
- Brainstem
Which of the following answers is/are correct?
a. both dopamine and NE are synthesised from tyrosine
b. CA synthesis: tyrosine–>L-DOPA–>dopamine–>NE–>epinephrine
c. Dopamine is synthesised from L-tyrosine and NE is synthesised from D-tyrosine
d. dopamine and serotonin are synthesised from tyrosine
e. all WAs are synthesised from tyrosine
a, b
what is the rate limiting step in dopamine synthesis?
Dopamine is synthesised from L-Tyrosine. different enzymes are involved in its synthesis, but the rate limiting step is the synthesis of L-DOPA from L-tyrosine by the enzyme Tyrosine hydroxylase using O2, Fe2+ and TBH as cofactors)
Tyrosine hydroxylase….(which of the following answers is/are correct)?
a. is an important enzyme but deficiency can be compensated by other enzymes
b. is a crucial enzyme- deficiency can be lethal
c. can also hydroxylate phenylalanine
d. uses Fe2+ as an electron donor
e. b, c, d are correct
e
where are DA and NE stored in the cell and how are thy transported?
in synaptic vesicles. transported into vesicles by VMAT
pathways of clearance of dopamine and NE…
- DAT- dopamin transporter- uptake of dopamine from the synaptic cleft
- NET - NE-transporter- uptake of NE from the cleft
–> after reuptake: inactivation of monoamines by MAO and COMT
in what ways can catecholamines get inactivated? what key molecules are involved in the process?
catecholamines inactivation occurs in 2 ways:
1. neuronal activity - not very efficient, but fluctuates as neurons fire more rapidly or slowly
- enzymatic inactivation- key enzymes: MAO and COMT; both can be localised intra or extracellularly and breakdown of CAs can occur also either within cell or in the cleft.
how can one test if CAs are metabolised properly?
monoamines are broken down into VHA and AMA. these can be used as markers for dopamine breakdown, by measuring the concentration in the cell after DA release.
what are the characteristics of CAs transporters (NET, DAT)?
- perisynaptic
- energy dependent
- depending on Na+ gradient across neuronal membrane (Na+/K+ ATPase)
- not dependent on Mg2+
- The main target of cocaine and amphetamines (block NET and DAT activity)
what is the target of reserpine? what is the outcome?
reserpine inhibits VMAT and depletes dopamine stores
what is the target of cocaine? what is the outcome?
cocaine blocks the DA transporter DAT –> increase in extracellular dopamine and overexcitation
what is the target of amphetamine? what is the outcome?
amphetamine binds VMAT and releases NT from vesicles. in addition, it interacts with CA transporters and reverses the activity of DAT and NET so dopamine and NE are RELEASED instead of being taken up.
