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Block 3 Pharm > Intro CNS II: Neurotransmitters > Flashcards

Intro CNS II: Neurotransmitters Flashcards

1
Q

Noradrenergic neurons (i.e. neurons that utilize norepinephrine) are located in the

A

medulla oblongata, pons and midbrain called the reticular activating system

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2
Q

a prototype catecholamine

A

Norepinephrine

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3
Q

Very important in arousal (wakefulness) and in regulation of autonomic functions like breathing and blood pressure

A

Nepi

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4
Q

Nepi must be made in the brain bc

A

can’t cross the BBB

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5
Q

Nepi is made from

A

tyrosine, taken across the BBB

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6
Q

tyrosine is converted to 3,4-dihydroxyphenylalanine (DOPA) by

A

tyrosine hydroxylase

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7
Q

DOPA is converted into dopamine by

A

DOPA decarboxylase

a) low substrate specificity

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8
Q

dopamine is converted into norepinephrine by

A

dopamine beta hydroxylase

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9
Q

Primary regulation of norepinephrine synthesis occurs via

A

tyrosine hydroxylase (TH)

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10
Q

TH is normally saturated with tyrosine so its activity is the rate limiting step for____ synthesis under basal conditions

A

DOPA

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11
Q

TH has an essential co-factor

A

tetrahydrobiopterine, BH4

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12
Q

Short-term regulation of tyrosine hydroxylase activity occurs via:

A

(1) phosphorylation at four different serine residues

(2) end-product (i.e. norepinephrine) inhibition of BH4 binding to the enzyme; this detects over-filled vesicles

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13
Q

Synthesis of Nepi is tightly regulated; seems designed to maintain a constant amount that is released:

A

in a single synpatic vesicle

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14
Q

Dopamine beta hydroxylase is located in______ and co released with_________

A

synaptic vessicles
with NE
(not well regulated)

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15
Q

DOPA decarboxylase has _____substrate specificity and is found in

A

LOW

serotonergic neruons like astrocytes

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16
Q

Tyrosine Hydroxylase is saturated with ______ at normal conc but not saturated with _____-

A

saturated with tyrosine

not saturated with tetrahydrobiopterine (BH4) co-factor

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17
Q

Activity of tyrosine hydroxylase is regulated by

A

binding of BH4

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18
Q

Where does the last step of synthesis of NE occur

A

Dopamine is taken into the vesicle, the last step of synthesis occurs there

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19
Q

Vesicular monoamine transporters are called VMAT; VMAT2 is found

A

in the brain

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20
Q

NE competes directly for BH4; the NE regulating BH4 binding is :

A

a specific regulatory pool present in cytosol

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21
Q

Neuronal activity increases _____, which then actiates CaM kinase which increases affinity for BH4

A

Calcium

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22
Q

What activates CaM kinsase

A

increase in neuronal activity–> increase in Ca++

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23
Q

What results in decreased affinity of TH for BH4

A

inhibition of cAMP generation and decreased PKA activity

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24
Q

Three mechanisms of norepinephrine release

A

a) calcium-dependent exocytosis of vesicles
b) reversal of plasma membrane transporters
c) dendritic release that is not calcium-dependent

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25
Q

Release of NE is regulated by presynaptic receptors (autoreceptors)

a) _______inhibits release
b) _______ increases releas

A

alpha2 receptor

beta receptor

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26
Q

alpha 2 presynaptic receptor will _____ NE release

A

inhibit

called feed back regulation

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27
Q

Beta receptor on the presynaptic terminal will _____ NE release

A

increase

called feed forward regulation

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28
Q

All transmitters can be inactivated by

A

diffusion

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29
Q

_____ by the presynaptic neuron is the most important: neuronal not astrocytic

A

Reuptake

30
Q

During reuptake:

High affinity carrier proteins move norepinephrine from _____ to ______ compartments

A

from extracellular to intracellular compartments

31
Q

During reuptake of NE, this is a E requiring process via

A

Na+ co transporter

32
Q

Reuptake for NE has a binding site for norepinephrine that is the site of action of _____

A

inhibitors

33
Q

Once norepinephrine is intracellular, it can be

A

re-packaged into vesicles for release or degraded by enzymes

34
Q

deaminates norepinephrine

A

Monoamine oxidase (MAO)

35
Q

which form of MAO is found in the brain

A

MAOB

36
Q

MEch of Catechol-O-methyl-transferase (COMT)

A

transfers a methyl group from S-adenosylmethionine to the meta OH of norepinephrine

37
Q

transfers a methyl group from S-adenosylmethionine to the meta OH of norepinephrine

A

Catechol-O-methyl-transferase (COMT)

38
Q

Two enZ inactivations of NE

A

MAO

COMT

39
Q

All 9 of the receptors for norepinephrine are

A

‘adrenergic’ G protein coupled

40
Q

how are NE receptors classified

A

using structure activity releationships

41
Q

Coupled to 2nd messenger that increases Ca++ and is found on non-neuronal cells in periphery

A

alpha 1

42
Q

alpha 1 receptors are coupled to ______ and will _____ Ca++ found in non-neuronal cells

A

2nd messengers

increase

43
Q

these inhibit adenyl cyclase and often present on presynaptic neourons; release-inhibiting autoreceptor

A

alpha 2

44
Q

alpha 2 receptors _____ adenyl cyclase, are on presynaptic side and are

A

inhbit

release inhibiting autoreceptors

45
Q

Beta receptors for NE will

A

increase adenly cyclase activity

46
Q

Beta receptors all work to increase adenyl cyclase, the dif in Beta subtypes is

A

the tissue they are located in

47
Q

What does adenyl cyclase do

A

generates cAMP and then activates PKA

48
Q

Via alpha receptors we see that NE will

A

induce arousal/stimuation and information gating or focus like a traffic controller

49
Q

Via beta receptors we see reguation of

A

sympathetic and PNS outflow such as BP control

50
Q

Neurotensin is what kind of NT

A

neuropeptide

51
Q

Neurotensis is ____ aa long and found in

A

13 aa long

prefrontal cortex and the hypothalamus in the midbrain

52
Q

Neurotensin is always co-localized with

A

DA—- these two transmitters are utilized by same neurons

53
Q

Seems that the peptides in general are _______ with other neurotransmitters and affect and are affected by these NTs.

A

co-localized

54
Q

It’s hypothesized that the neuropeptides add _______ to the simple signaling that could occur with a single transmitter

A

complexity, (“color”)

55
Q

Co-transmission is a ___ and a ____

A

peptide and amine

56
Q

Transmitting signals are different, not

A

redundant

57
Q

Neurotensin starts as a _____ aa and then hydrophobic signal sequence will direct the protein to

A

170

to the ER

58
Q

At the Gogli, neurotensin is:

A

packed into secretory vesicles that containe peptidases where it’s processed to one molecule of neurotensin and one neurmedin N

59
Q

What results from going 170 precursorr of neurtoensin

A

processed in the golgi by peptidases to one Neurotensin and one neuromedin N

60
Q

Neurotensin is stored in different type of vesicles that are NOT synaptic vesicles but are

A

secreatory vesicles: dense core

61
Q

dense core secreatory vesicles for Neurotensin are smaller or larger then synpatic vesicles

A

larger

62
Q

Neurotensin secreatory vesicles are transported to axons via

A

secratory path

63
Q

Neurotensin secreatory vesicles concentration as terminals

A

low, variable

64
Q

Release of Neurotensin is ________, but require high intensity, rapid firing of neurons to be released

A

calcium dependent

65
Q

What is special about neurotensin release

A

Release is not necessarily at the active zone; can be released anywhere along the membrane and is not recaptured

66
Q

Regulation of inactivation of neurotensin

A
  1. Nonselective peptidases cleave the peptide
  2. Diffusion
  3. No reuptake by transporters
    a) However, peptide bound to receptor can be internalized along with the receptor and is transported up to the cell body and may be functional there
67
Q

peptides tend to _______that is, they are more persistent at their receptors than the amine neurotransmitters

A

“last longer”;

68
Q

Compared to the inactivation of glutamate, inactivation of neorotensin is:

A

more haphazard,

singnaling is LESS directed and can last longer with lower fidelity

69
Q

Receptors for Neurotensin

A

GCRP with many bonds bc neurtensin is so large and will have higher affinity binding

70
Q

The higher affinity binding and more bonds forming btw neurotensin and R may compensate for:

A

lower amounts released and distance needed to travel

Block 3 Pharm (19 decks)

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