Lecture 36: Neuropharm, Catecholamines and Sympathetic NS

Question 1

What is neurotransmitter of parasympathetic system?

Answer 1

ACh

Question 2

What is only sympathetic innervation that has Ach as postganglionic neurotransmitter?

Answer 2

Sweat glands

Question 3

What is sympathetic nervous systems association with psychiatry?

Answer 3

SNS regulates mood and attention

Question 4

What are the primary neurotransmitters of sympathetic nervous system?

Answer 4

1. NE
2. epinephrine
3. Dopamine
4. Serotonin
   Can be unique and all together

Question 5

What are the cotransmitters that are used to modulate the primary neurotransmitters of sympathetic system?

Answer 5

1. ATP
2. Galanin
3. Neuropeptide Y

Question 6

What is the significance of neuropeptide Y?

Answer 6

A cotransmitter of sympathetic NS

Question 7

What is the significance of Galanin?

Answer 7

A cotransmitter (neuropeptide) of sympathetic NS

Question 8

What is the significance of ATP for neurotransmission?

Answer 8

A cotransmitter of sympathetic NS

Question 9

What is the rate-limiting step in the biosynthesis of catecholamines? How is it regulated?

Answer 9

Rate limiting step = tyrosine to dopa by tyrosine hydroxylase
Regulation by phosphorylation (PKA and PKC signaling pathway): acute mechanism for increasing synthesis
-delayed increase in tyrosine hydroxylase gene expression after nerve stimulation

Question 10

Why is it important to memorize synthesis of catecholamines?

Answer 10

Targets for therapy

Question 11

What neurotransmitter is Tryptophan a precursor for?

Answer 11

Serotonin

Question 12

What neurotransmitter is TYROSINE a precursor for?

Answer 12

Dopamine, NE and epinephrine

Question 13

What is the difference between serotonin and dopamine, ne and epinephrine synthesis?

Answer 13

Serotonin starts with tryptophan

The others start with TYROSINE

Question 14

What is the order of synthesis of catecholamines?

Answer 14

1. Tyrosine
2. DOPA
3. Dopamine
4. Norepinephrine
5. Epinephrine

Question 15

What is the enzyme that converts tyrosine to DOPA? Significance?

Answer 15

Tyrosine hydroxylase

Rate-limiting step

Question 16

Tryptophan hydroxylase is the rate limiting step for

Answer 16

Serotonin synthesis

Question 17

Tyrosine hydroxylase is rate limiting step for

Answer 17

Dopamine synthesis

Question 18

What is the enzyme that that converts Dopa to Dopamine?

Answer 18

i-Aromatic amino acid DECARBOXYLASE

Question 19

What is the enzyme that converts dopamine to NE?

Answer 19

DOPAMINE Beta-hydroxylase

Question 20

What is the enzyme that converts NE to epinephrine?

Answer 20

Phenylethanolamine N-methyltransferase (PNMT)

Mnemonic: Phenylethanolamine is another name for NE lol

Question 21

Phenylethanolamine N-methyltransferase (PNMT)

Mnemonic: Phenylethanolamine is another name for NE lol

Answer 21

Enzyme that converts dopa to dopamine

Question 22

What is phenylethanolamine N-methyltransferase?

Answer 22

Enzyme that converts NE to E

Question 23

What leads to increase of catecholamine synthesis?

Answer 23

Stress!

Fight or Flight

Question 24

What is contained in catecholaminergic vesicles?

Answer 24

catecholamines, ATP, dopamine beta hydroxylase, ascorbic acid and NPY

Question 25

What is negative feedback loop of catecholamines?

Answer 25

Large amount of dopamine and NE can inhibit tyrosine hydroxylase

Question 26

What are the two cell types of adrenal medulla?

Answer 26

1. those with norepinephrine only (no phenylethanolamine-N-methyltransferase…PNMT) 2. those with primarily epinephrine (DOES contain PNMT)

Question 27

How is PNMT regulated?

Answer 27

It is regulated by glucocorticoids (cortisol) secreted by adrenal cortex

Question 28

What does the adrenal cortex secrete?

Answer 28

Glucocorticoids (cortisol)

Question 29

What does the adrenal medulla secrete?

Answer 29

Catecholamines | NE and epinephrine

Question 30

How are catecholamines stored?

Answer 30

In nerve endings, catecholamines are stored in vesicles where they are protected from degradation -in adrenal medulla, they are stored in granules

Question 31

Is the vesicle reuptake energy dependent or not? Significance?

Answer 31

It IS ATP dependent | Significant because ATP can be taken up and can be ratelimiting

Question 32

How do you release catecholamines?

Answer 32

-membranes also allow slow leakage of amines out of vesicles -but this is inconsequential Exocytotic release of vesicle contents is CALCIUM dependent

Question 33

How does calcium regulate release vesicles?

Answer 33

Membrane bound Ca channel regulates intracellular Ca Ca interacts with vesicle associated membrane proteins (VAMP) and triggers fusion of the vesicular membrane with the terminal membrane and release of norepinephrine

Question 34

What is the significance of vesicle associated membrane proteins (VAMP)?

Answer 34

VAMP interacts with Ca to mediate vesicle release

Question 35

What are autoreceptors (heteroreceptors)?

Answer 35

Sit on presynaptic terminal A receptor on the PREsynaptic terminal that binds to the neurotransmitters -binding of neurotransmitter…depending on the autorecptor…brings about different responses in terminal bouton

Question 36

What happens when neuroepinephrine binds to alpha2-adrenergic autoreceptor? Beta-adrenergic autoreceptor?

Answer 36

Negative feedback of vesicle formation | Positive feedback for vesicle formation

Question 37

What is important in GCPR?

Answer 37

The g-protein subunit determines the effect (Gq, Gi, Gs)

Question 38

What are the different types of adrenoreceptors?

Answer 38

``` Alpha-1 = Gq = increase Ca Alpha -2 = Gi = decrease cyclic AMP Betas are (Gs) so increase cAMP ```

Question 39

What do all receptor types except for | Beta-2 (Gs) bind to?

Answer 39

Both NE and E | Beta-2 only binds to Epi

Question 40

What are the major factors determining actions of sympathomimetic amines?

Answer 40

1. Relative potency of amine 2. Proportion and density of various receptors - whether or not you have more or less alpha vs. beta receptors…predicates the response in any given tissue 3. Reflex or homeostatic adjustments made in response to actions produced by amine e. g. acting like a man instead of squealing when you see a mouse 4. refractoriness/desensitization of the receptor e. g.Beta-arrestin will internalize receptors and terminate ligand-receptor affinity

Question 41

What is refractoriness?

Answer 41

Refers to once b-arrestin is there, you can’t bind the ligand

Question 42

What gets transported via VMAT into vesicle?

Answer 42

Dopa gets converted to dopamine and is transported by VMAT into a vesicle