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B&B Week 7 Flashcards > Lecture 36: Neuropharm, Catecholamines and Sympathetic NS > Flashcards

Lecture 36: Neuropharm, Catecholamines and Sympathetic NS Flashcards

1
Q

What is neurotransmitter of parasympathetic system?

A

ACh

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2
Q

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

A

Sweat glands

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3
Q

What is sympathetic nervous systems association with psychiatry?

A

SNS regulates mood and attention

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4
Q

What are the primary neurotransmitters of sympathetic nervous system?

A
  1. NE
  2. epinephrine
  3. Dopamine
  4. Serotonin
    Can be unique and all together
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5
Q

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

A
  1. ATP
  2. Galanin
  3. Neuropeptide Y
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6
Q

What is the significance of neuropeptide Y?

A

A cotransmitter of sympathetic NS

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7
Q

What is the significance of Galanin?

A

A cotransmitter (neuropeptide) of sympathetic NS

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8
Q

What is the significance of ATP for neurotransmission?

A

A cotransmitter of sympathetic NS

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9
Q

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

A

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

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10
Q

Why is it important to memorize synthesis of catecholamines?

A

Targets for therapy

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11
Q

What neurotransmitter is Tryptophan a precursor for?

A

Serotonin

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12
Q

What neurotransmitter is TYROSINE a precursor for?

A

Dopamine, NE and epinephrine

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13
Q

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

A

Serotonin starts with tryptophan

The others start with TYROSINE

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14
Q

What is the order of synthesis of catecholamines?

A
  1. Tyrosine
  2. DOPA
  3. Dopamine
  4. Norepinephrine
  5. Epinephrine
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15
Q

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

A

Tyrosine hydroxylase

Rate-limiting step

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16
Q

Tryptophan hydroxylase is the rate limiting step for

A

Serotonin synthesis

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17
Q

Tyrosine hydroxylase is rate limiting step for

A

Dopamine synthesis

18
Q

What is the enzyme that that converts Dopa to Dopamine?

A

i-Aromatic amino acid DECARBOXYLASE

19
Q

What is the enzyme that converts dopamine to NE?

A

DOPAMINE Beta-hydroxylase

20
Q

What is the enzyme that converts NE to epinephrine?

A

Phenylethanolamine N-methyltransferase (PNMT)

Mnemonic: Phenylethanolamine is another name for NE lol

21
Q

Phenylethanolamine N-methyltransferase (PNMT)

Mnemonic: Phenylethanolamine is another name for NE lol

A

Enzyme that converts dopa to dopamine

22
Q

What is phenylethanolamine N-methyltransferase?

A

Enzyme that converts NE to E

23
Q

What leads to increase of catecholamine synthesis?

A

Stress!

Fight or Flight

24
Q

What is contained in catecholaminergic vesicles?

A

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

25
Q

What is negative feedback loop of catecholamines?

A

Large amount of dopamine and NE can inhibit tyrosine hydroxylase

26
Q

What are the two cell types of adrenal medulla?

A
  1. those with norepinephrine only (no phenylethanolamine-N-methyltransferase…PNMT)
  2. those with primarily epinephrine (DOES contain PNMT)
27
Q

How is PNMT regulated?

A

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

28
Q

What does the adrenal cortex secrete?

A

Glucocorticoids (cortisol)

29
Q

What does the adrenal medulla secrete?

A

Catecholamines

NE and epinephrine

30
Q

How are catecholamines stored?

A

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

31
Q

Is the vesicle reuptake energy dependent or not? Significance?

A

It IS ATP dependent

Significant because ATP can be taken up and can be ratelimiting

32
Q

How do you release catecholamines?

A

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

33
Q

How does calcium regulate release vesicles?

A

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

34
Q

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

A

VAMP interacts with Ca to mediate vesicle release

35
Q

What are autoreceptors (heteroreceptors)?

A

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

36
Q

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

A

Negative feedback of vesicle formation

Positive feedback for vesicle formation

37
Q

What is important in GCPR?

A

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

38
Q

What are the different types of adrenoreceptors?

A 
Alpha-1 = Gq = increase Ca
Alpha -2 = Gi = decrease cyclic AMP
Betas are (Gs) so increase cAMP
39
Q

What do all receptor types except for

Beta-2 (Gs) bind to?

A

Both NE and E

Beta-2 only binds to Epi

40
Q

What are the major factors determining actions of sympathomimetic amines?

A
  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
41
Q

What is refractoriness?

A

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

42
Q

What gets transported via VMAT into vesicle?

A

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

B&B Week 7 Flashcards (16 decks)

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