Lecture 7: Catecholamines 1

Question 1

Explain Catecholamine Synthesis

Question 2

Explain Catecholamine Release

Question 3

Explain Catecholamine Inactivation

Question 4

Describe the Organization of the Dopaminergic System

Question 5

Describe the Function of the Dopaminergic System

Question 6

Describe the processes involved in catecholamine synthesis

Question 7

Describe the processes involved in catecholamine storage

Question 8

Describe the processes involved in catecholamine release.

Question 9

Explain how catecholamines are inactivated using reuptake.

Question 10

Explain how catecholamines are inactivated using metabolism.

Question 11

List and explain the clinical uses of drugs that act on catecholamine metabolism.

Question 12

List and explain the clinical uses of drugs that act on catecholamine reuptake.

Question 13

Name the major ascending dopaminergic pathways that originate in the midbrain

Question 14

Identify the locations of the cell bodies and the projection areas of each dopaminergic pathway.

Question 15

Explain the role of DA in behavioral regulation, using initiation and control of voluntary movement

Question 16

Explain the role of DA in behavioral regulation using responses to rewarding stimuli

Question 17

Explain the role of DA in behavioral regulation using cognitive functioning.

Question 18

What are the members of the family of DA receptors

Question 19

Describe the family of DA receptors’ various subtypes

Question 20

Describe the family of DA receptors’ signaling mechanisms

Question 21

Describe the family of DA receptors’ roles as postsynaptic receptors

Question 22

Describe the family of DA receptors’ roles as autoreceptors.

Question 23

Describe the behavioral effects of DA receptor agonists

Question 24

Describe the behavioral effects of DA receptor antagonists

Question 25

Describe the physiological effects of DA receptor agonists

Question 26

Describe the physiological effects of DA receptor antagonists

Question 27

Describe DA receptor clinical applications

Question 28

What are catecholamines?

Answer 28

Catecholamines are monamines: a catechol + amine group

Question 29

What are the different types of catecholamines?

Answer 29

1. Dopamine (DA) 2. Norepinephrine (NE) 3. Epinephrine (EPI)

Question 30

What are the adjective forms of the catecholamines?

Answer 30

dopaminergic, noradrenergic, and adrenergic

Question 31

What secretes from the adrenal medulla and what do they act as?

Answer 31

Adrenal medulla secretes EPI and NE into the bloodstream where they act as hormones.

Question 32

How are catecholamines synthesized?

Answer 32

By a multistep pathway in which tyrosine hydroxylase catalyzes the rate-limiting step

Question 33

What are catecholamines synthesized from?

Answer 33

tyrosine

Question 34

What is Tyrosine hydroxylase (TH)

Answer 34

the rate-limiting enzyme

Question 35

What factor affects TH activity with negative feedback?

Answer 35

DA and NE levels in the nerve terminal

Question 36

What factor stimulates TH activity?

Answer 36

Cell firing stimulates TH activity through phosphorylation of the enzyme by protein kinases

Question 37

How is tyrosine obtained?

Answer 37

Tyrosine is obtained from dietary protein, transported from blood to brain

Question 38

How can catecholamine synthesis be increased?

Answer 38

By administering precursors such as tyrosine or l-DOPA

Question 39

What is used to treat Parkinson’s disease?

Answer 39

l-DOPA

Question 40

What is each step of synthesis dependent on?

Answer 40

specific enzymes – dependent on neuron EX: If neurons use DA as NT, only contain TH and AAAD If neurons need NE, also possess DBH

Question 41

What do drugs that reduce synthesis do?

Answer 41

inhibit one of the enzymes

Question 42

What is the drug that blocks TH?

Answer 42

α-methyl-para-tyrosine (AMPT)

Question 43

What are the steps in synthesis called?

Answer 43

synthetic pathways

Question 44

What do synthetic pathways do?

Answer 44

provides a mechanism for regulating the amount of transmitter available for release

Question 45

What opportunity is possible with synthetic pathways?

Answer 45

to intervene with drugs that alter transmitter synthesis in specific ways.

Question 46

What catalyzes conversion of dopamine to norepinephrine?

Answer 46

dopamine β-hydroxylase (DBH)

Question 47

What catalyzes conversion of DOPA to dopamine?

Answer 47

Aromatic amino acid decarboxylase (AADC)

Question 48

What is catecholamine storage and release regulated by?

Answer 48

vesicular uptake autoreceptor activity cell firing rate

Question 49

What are catecholamines loaded into synaptic vesicles by?

Answer 49

vesicular monoamine transporters (VMAT)

Question 50

What can VMAT be blocked by?

Answer 50

reserpine (snake root)

Question 51

What is snake root and what symptoms can it cause?

Answer 51

an irreversible inhibitor; (reduces the amount of NT at the terminal) causes sedation and depressive symptoms

Question 52

What are reversible inhibitors of VMAT used for?

Answer 52

To reduce uncontrolled movements in Huntington’s disease and tardive dyskinesia.

Question 53

Where is VMAT1 found?

Answer 53

adrenal medulla

Question 54

Where is VMAT2?

Answer 54

present in the brain

Question 55

What do VMAT1 and VMAT2 have in common?

Answer 55

Both can be blocked by reserpine.

Question 56

What are some reversible VMAT2 inhibitors?

Answer 56

tetrabenazine (trade name Xenazine), deutetrabenazine (Austedo), and valbenazine (Ingrezza)

Question 57

What makes TH the rate limiting enzyme?

Answer 57

Tyrosine to DOPA by TH occurs slower

Question 58

What stimulates TH activity?

Answer 58

Neuronal firing

Question 59

What determines the overall rate of DA or NE formation?

Answer 59

Tyrosine Hydroxylase

Question 60

What regulates the activity in the neurons of the dopaminergic system?

Answer 60

the amount of DA/NE present at the terminal, negative feedback when high.

Question 61

What is done to TH by second messengers, what are they, and what do they do?

Answer 61

TH can be phosphorylated by a number of secondary messengers (PKA, PKC, CaMKII). Generally increases the enzyme activity.

Question 62

How can you increase the formation of TH?

Answer 62

by increasing precursors such as tyrosine and L-DOPA.

Question 63

What is Tyrosine administration used for?

Answer 63

Enhancing cognitive functions e.g. memory

Question 64

What is L-DOPA the primary therapeutic agent for?

Answer 64

treating Parkinsons

Question 65

What does a typical dopaminergic neuron’s membrane possess?

Answer 65

Autoreceptors. When these receptors are stimulated, they inhibit sub¬sequent DA release by the cell.

Question 66

What are some psychostimulants and what do they do?

Answer 66

Psychostimulants amphetamine and methamphetamine cause release of catecholamines without nerve firing. Lab animals show increased activity.

Question 67

What type of behaviors occur with high doses of psychostimulants and what are they?

Answer 67

Stereotyped behaviors include intense sniffing, repetitive head and limb movements, and licking and biting.

Question 68

What are human side effects of psychostimulants?

Answer 68

In humans, drug effects include increased alertness, high energy levels, euphoria, insomnia

Question 69

What release is impacted by autoreceptors and how?

Answer 69

DA release is inhibited by autoreceptors

Question 70

What also influences DA release?

Answer 70

Neuron firing pattern

Question 71

What is the first way neuron firing impacts DA release?

Answer 71

Single-spiking mode: action potentials appear at irregular intervals (tonic release)

Question 72

What is the second way neuron firing impacts DA release?

Answer 72

Burst mode: trains of 2–20 spikes at higher frequency (phasic release); transmitter release occurring faster than it can be cleared and/or metabolized.