catecholamines 1

Question 1

catecholamines

Answer 1

Dopamine (DA), Norepinephrine (NE) and Epinephrine (EPI), all monoamines made from tyrosine

Question 2

where are NE and EPI released?

Answer 2

adrenal medlla

Question 3

how are catecholamines made?

Answer 3

tyrosine + tyrosine hydroxylase (TH) -> L DOPA, LDOPA + dopamine decarboxylase (AADC) -> DA
DA + dopamine beta hydroxylase (DBH) -> NE

Question 4

what is the rate limiting step in DA synthesis?

Answer 4

tyrosine + tyrosine hydroxylase (TH) -> L DOPA, can avoid by supplementing LDOPA

Question 5

TH activity is regulated by: pharmacology:

What pharmacological factors help to regulate TH activity?

Answer 5

high catecholamine levels inhibit TH activity through phsphorylation / dephosphroylation; negative feedback
pharmacology:
L-DOPA: precursor of rate limiting step, orally active, can go through BBB
AMPT: blocks TH and prevents synthesis of L DOPA; induces sedation, depression, reduced blood pressure; can be reversed with L-DOPA

Question 6

Catecholamine packing needs VMAT (vesicular monoamine transporter), which can be affected by

Answer 6

Reserpine blocks VMAT and prevents DA/NE from being packages; if not protected, they are broken down by enzymes in terminals; causes sedation and depression and systemic effects

Question 7

what are MAO and COMT

Answer 7

monoamine oxidase and catechol-O-methyltransferase; they metabolize catecholamines

Question 8

HVA (homovanillic acid) is

Answer 8

main metabolite of DA; if you find a lot of this, that means DA is being used

Question 9

MHPG is

Answer 9

NE metabolite; enters CSF and bloodstrem; elimited via urine

Question 10

MAO inhibitor

Answer 10

phenelzine (nardil), used to treat clinical depression

Question 11

COMT inhibitor

Answer 11

tolcapone (tasmar) enhances the effectiveness of L-DOPA in treating later parkinson stages

Question 12

en passant synapses

Answer 12

many DA and NE neurons have repeated swellings (varicosities) filled with synaptic vesicles that form ENPASSANT “in passing” snypses, allows for widespread transmission of signal

Question 13

DA and NE membrane transporter proteins

Answer 13

are referred to as DAT and NET; removed from synaptic cleft with membrane transporer proteins; they are sloppy. In frontal lobes, most DA reuptake done by NET

Question 14

catecholamine reuptake pharmacology

Answer 14

blocking transporter leads to greater extracellular neurotrasmitter levels (due to lack of reuptake)
Cocain inhibits reuptake of all monoamines (DA, NE, 5HT)
Tricyclic antidepressants inhibit NE and 5HT
methylphenidate (ritalin) is more selective for catecholamines

Question 15

normal catecholamine transmission

Answer 15

DA/NE is released from presynaptic terminal by exocytosis when an impulse reaches terminal, and the NT is quickly taken back by reuptake transporter

Question 16

amphetamine pharmacological effects

Answer 16

reverses the DA / NE tranporter; instead of taking them back up they now release more; transmitter release independent of cell firing; also not selective: act on DA, NE and 5HT

Question 17

amphetamine behavioural effects: locomotion

Answer 17

increase locomotor activity by increasing DA in nucleus accumbens (ventral striatum); at higher doses, methamphetamine tweaking instead - lower doses saturate DA release in accumbus but higher doses -> more DA activation in dorsal straitum

Question 18

amphetamine behavioural effects: sensitization

Answer 18

sensitization: repeated exposure increases sensitivity to effect of drug;

Question 19

Amphetamine (AMPH)-induced locomotion

Answer 19

Gets low dose AMPH on Day 1 (test dose), then gets daily saline injections for 5 days
Gets test dose AMPH on Day 1, then gets AMPH repeatedly for 5 days
On test day, both groups get same test dose of amphetamine again

Question 20

stimulant and cognitive enhancers

Answer 20

lower dose d-amphetamine can have therapeutic effects:
powerful stimulant: promote wakefulness but reduce REM sleep
cognitive enhancer: for multiple forms of cognition

side effect: lacking creative thought

Question 21

catecholamine autoreceptors

Answer 21

DA and NE have D2 and a2 respectively;
monoamine autoreceptors reside on axon terminals and cell bodies
activation enhances opening of voltage gated K+ channels that shorten durations of action potentials
on terminals, this reduces Ca+ influx and transmitter exocytosis
autoreceptors on CELL BODIES reduce neural firing

Question 22

Catecholamine autoreceptors

Answer 22

For DA (or other monoamine) neuron
Firing at cell body causes “somatodendritic” release
Local release acts on somatodendritic autoreceptors to reduce neural firing
Terminal autoreceptor stimulation reduces transmitter release

Question 23

Selective knockout of D2 autoreceptors (but not postsynaptic D2) in animals leads to

Answer 23

greater DA-mediated locomotion vs controls - confirming these receptors attenuate DA transmission

Question 24

lower dose DA / NE saturate ————, but higher dose do ————-

Answer 24

Lower dose saturates autoreceptors (reducing transmitter release), but does not activate enough postsynaptic receptors to affect neuron
Higher dose activate sufficient # of postsynaptic receptors