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House Pharmacology > Acetycholine Synthesis, Storage Release > Flashcards

Acetycholine Synthesis, Storage Release Flashcards

1
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Acetylcholine

A

Amine

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2
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Dopamine

A

Amine

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3
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Norepinephrine

A

Amine

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4
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Epinephrine

A

Amine

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5
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Serotonin

A

Amine

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6
Q

Neurotransmitters

Answer with amine, peptide or amino acid

GABA

A

Amino acid

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7
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Glutamic acid

A

Amino acid

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8
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Glycine

A

Amino acid

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9
Q

Neurotransmitters

Answer with amine, peptide or amino acid

CCK

A

Peptide

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10
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Neuropeptide Y

A

Peptide

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11
Q

Somatostatin is a neurotransmitter

T/F

A

T

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12
Q

Substance P is a neurotransmitter

T/F

A

T

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13
Q

Vasopressin is a neurotransmitter

T/F

A

T

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14
Q

Neurotransmitters

Answer with amine, peptide or amino acid

TRH
CRH

A

Peptide
Peptide

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15
Q

Neurotransmitters

Answer with amine, peptide or amino acid

Enkephalins
Endorphins

A

Peptide
Peptide

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16
Q

vasoactive intestinal peptide is not a neurotransmitter

T/F

A

F

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17
Q

Ach is responsible for ALL motor transmission in vertebrates

T/F

A

T

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18
Q

Ach mediates _____pathetic actions of the ANS

A

Parasympathetic

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19
Q

Both pre ganglionic fibers of sympathetic and parasympathetic nervous system are myelinated

T/F

A

T

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20
Q

Functions of Ach in the CNS
• Basal Forebrain:
-______________
-_____________
–_________ Disease

A

arousal and attention; Learning and memory

Alzheimer

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21
Q

Functions of Ach in the CNS

• Parabrachial nucleus
-__________
– (Stop or Continue?) to fire during REM
– # Cells correlate with REM sleep

A

REM sleep

Continue

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22
Q

Functions of Ach in the CNS

• striatum- ____________

•______ and other sensory input

A

Reward and Addiction

Pain

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23
Q

Functions of Ach in the PNS

• Vasculature (endothelial cells) – Release of _____________(____) and vaso______
• Eye iris (pupillae sphincter muscle) – (Contraction or Dilation ?) and _______

A

endothelium-derived relaxing factor ; NO

dilation

Contraction; miosis

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24
Q

Functions of Ach in the PNS

• Ciliary muscle – (Contraction or Dilatation?) and accommodation of lens to (far or near?) vision

• Salivary and lacrimal glands – Secretion is (thick or thin?) and (mucous or watery?)

A

Contraction

Near vision

Thin

Watery

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25
Q

Functions of Ach in the PNS

• Bronchi – (Constriction or Dilation?) , (increased or decreased?) secretions

• Heart – ___cardia, ___eased conduction (AV ___ at high doses), (positive or negative?) ____tropic action

A

Constriction

Increased

Brady; decreased; block ; negative inotropic

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26
Q

Functions of Ach in the PNS

• GIT – ____eased tone, ___eased secretions, (constriction or relaxation?) at sphincters

• Urinary bladder – (Contraction or Relaxation ?) of detrusor muscle, (Contraction or Relaxation ?) at sphincters

A

Incr; incr; relaxation

Contraction ; relaxation

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27
Q

Functions of Ach in the PNS

• Sweat glands – (excessive or diminished?) sweating.

• Reproductive tract, male – ______

A

Excessive

Erection

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28
Q

Diaphoresis = _________

A

sweating more than normal or you’re sweating for no clear reason.

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29
Q

Functions of Ach in the PNS

• Uterus – variable , depending on _________

A

hormonal influence

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30
Q

Ach at the NMJ

• Regulated release of Ach causes muscle ___polarization: _____ or ______
– (Contraction or Relaxation?) of muscle

A

De

mEPP or EPSP

Contraction

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31
Q

_______ + ______ = acetylcholine

_____ enzyme helps

A

Acetyl coA

Choline

Choline acetyltransferase

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32
Q

Acetylcholine is broken down to _____ and ———- by ____ enzyme

A

Acetate

Choline

Acetylcholine esterase

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33
Q

Acetyl coA is gotten from _____ with the help of _____

A

Pyruvate

PDH complex

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34
Q

Choline acetyltransferase is inhibited by __________

A

Mercurials

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35
Q

Acetylcholine esterase is inhibited by _______ agents eg _____

A

Nerve

Sarin

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36
Q

Choline is replenished by ______ or _____

A

Reputake

Diet

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37
Q

________ loads acetylcholine into a vesicle

A

Vesicular acetylcholine transporter

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38
Q

_______ loads choline back into the nerve or into the vesicle

A

High affinity Choline transporter

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39
Q

Ach Equilibrium

• (choline)+(Acetyl-CoA) ——> Ach + (CoA)

– Availability of choline (CHT) drives rxn to the (left or right?)
– Decrease in Ach will cause shift in equilibrium (no substrate for reverse rxn)

A

Right

40
Q

Ach levels are extremely (stable or unstable?) over a wide range of neural activity

A

Stable

41
Q

Ach Release
• Action potential arrives at _______ terminal, __polarizing the membrane
• _____ ionmust be present for Ach to be released and have any effect

A

pre-synaptic

de

Ca2+

42
Q

Other Factors that Affect Ach Release
• Trophic factors
-NGF exerts (slow or rapid?) (short or long?) term effects on Ach synthesis and release
•________ (other hormones?)

A

Rapid; short

Estrogen

43
Q

Estrogen decreases ChAT levels

T/F

A

F

Increases

44
Q

Acetylcholinesterases

•_______ and ——- of acetylcholine
• Prevents ________ receptor
• Critical for recycling _____

A

Hydrolysis and deactivation

acetylcholine reactivating

choline

45
Q

Acetylcholinesterases

• Limits ________ events/ _____

A

Receptor signaling ; duration

46
Q

Acetylcholine esterases are Found in (intra or extra?) cellular space, ______

A

Extra ; synaptic cleft

47
Q

Acetylcholine esterase is a marker of cholinergic cells

T/F

A

F

It is not

48
Q

Inhibitors of AchE
–_______ disease
–_____,_______
_ Bioterrorism

A

Alzheimer

Glaucoma, myasthenia gravis

49
Q

______ is a drug used to treat dementia of the Alzheimer’s variety

A

Aricept

50
Q

Inhibition of storage of acetylcholine : ______

A

Vesamicol

51
Q

Inhibition of release of ach could be by _______

A

Botulinum
Or
Aminoglycosides

52
Q

ACETYLCHOLINE was the second neurotransmitter discovered

T/F

A

F

first

53
Q

ACETYLCHOLINE:

  • Was originally described as “ _______ stuff” by Otto Loewi because of its ability to ______________________________.
A

vagus

mimic the electrical stimulation of the vagus nerve

54
Q

In the autonomic nervous system, acetylcholine (ACh) is the neurotransmitter in the preganglionic ______________________ neurons.

A

sympathetic and parasympathetic

55
Q

In the autonomic nervous system, acetylcholine (ACh) is the neurotransmitter at all the ________pathetic innervated organs.

A

parasym

56
Q

In the autonomic nervous system, acetylcholine (ACh) is the neurotransmitter in the following sympathetic ANS

The _________.
The _______ glands.
__________ muscle

A

adrenal medulla

sweat

Piloerector

57
Q

In the peripheral nervous system, ACh is the neurotransmitter at the __________ junction between the ________ and ________.

A

neuromuscular

motor nerve and skeletal muscle

58
Q

In the central nervous system, ACh is found primarily in ____________

• A few important long-axon cholinergic pathways have also been identified.

Noteworthy is the cholinergic projection from the ___________ of ________ (in the _____________) to the _________ ________ and associated limbic structures

A

interneurons

nucleus basalis of Meynert

basal forebrain

forebrain neocortex

59
Q

Degeneration of this pathway between the nucleus basalis of Meynert to the forebrain neocortex is one of the pathologies associated with __________ disease.

A

Alzheimer’s

60
Q

Acetylcholine is synthesized in nerve terminals from _____________ and __________.

Acetylation is through the help of ATP in a reaction catalyzed by _____________ present in the axoplasm.

A

acetyl coenzyme A

choline

choline acetyltransferase (CAT)

61
Q

acetyl CoA is synthesized from ________

A

Glucose

62
Q

Choline is present in plasma at a concentration of about ______ and is taken up into cholinergic neurons by a _______-affinity ___________ transporter.

About _________ molecules of ACh are packaged into each vesicle by a _____________

A

10 mM

high; Na+/choline

10,000; vesicular ACh transporter.

63
Q

Both CAT and ACh may be found throughout the neuron, but their highest concentration is in __________.

A

axon terminals

64
Q

The presence of __________ is the “marker” that a neuron is cholinergic, only cholinergic neurons contain _____.

A

CAT

CAT

65
Q

The rate-limiting step in ACh synthesis is the ____________.

A

uptake of choline

66
Q

Uptake of choline is blocked by ______________.

A

HEMICHOLINIUM

67
Q

Organic _________ compounds, such as ______________, have a high affinity for sulfhydryl groups, which causes dysfunction of the enzyme choline acetyltransferase. This inhibition may lead to _______ deficiency and can have consequences on _____ function.

A

mercurial

methylmercury

ACH

motor

68
Q

During increased neuronal activity the availability of acetyl-CoA from the ____________ is ____regulated as is the uptake of choline into the nerve ending from the ___________.

______ ion appears to be involved in both of these regulatory mechanisms.

A

mitochondria; up

synaptic cleft

Ca2+

69
Q

The inactivation of ACh yields _______ and ___________.

A

choline

acetic acid.

70
Q

much of the choline used for ACh synthesis comes from the ____________________.

Another source is the breakdown of the _________, —————— .

A

recycling of choline from metabolized ACh

phospholipid, phosphatidylcholine

71
Q

• The uptake of ACh into the storage vesicle occurs through an energy- (dependent or independent ?) pump that (acidifies or alkalinizes?) the vesicle.

• The (acidified or alkalinized?) vesicle then uses a _________ transporter (______) to exchange ________ for ACh molecules.

•____________ blocks this carrier molecule.

A

Dependent; acidifies

acidified; vesicular ACh

VAChT; protons

VESAMICOL

72
Q

Release of ACh from nerve terminals occurs in (small or large?) quanta – the amount contained in individual vesicles is extruded by ______________.

Response to a nerve AP synchronous release of multiple quanta triggers postjunctional events.

A

Small; exocytosis

73
Q

Two toxins interfere with cholinergic transmission by affecting release:

  • ___________ toxin inhibits release.
  • ____________________ induces massive release and depletion.
A

Botulinum

Black widow spider venom (BWSV)

74
Q

Botulinum toxin A & B:

Are highly potent ____toxins produced by _____________ responsible for botulism.

They cause a (short or long?) -lasting loss of cholinergic transmission by interacting with ____________ involved in the ____________ of ACh.

A

exo; Clostridium botulinum

long; axonal proteins

exocytotic release

75
Q

Localized injection of a small quantity of botulinum toxin is useful for treating several ________ and other neurological conditions caused by ————- of cholinergic nerves.

A

spastic

overactivity

76
Q

In contrast to most other small-molecule neurotransmitters, the postsynaptic action of ACh at many cholinergic synapses (the neuromuscular junction in particular) are not terminated by ________ but by a powerful _______ enzyme, ______________.

A

reuptake; hydrolytic

acetylcholinesterase (AChE)

77
Q

AChE

This enzyme is concentrated in the ___________, ensuring a rapid decrease in ACh concentration after its release from the presynaptic terminal.

A

synaptic cleft

78
Q

AChE has a very (low or high?) catalytic activity (about _____ molecules of ACh per AChE molecule per second) and hydrolyzes ACh into acetate and choline.

A

High

5000

79
Q

The active site of AChE comprises two subsites:
- the ________ site
- the ________ subsite.

A

Anionic

esteratic

80
Q

The anionic subsite of AChE accommodates the ____________ amine of acetylcholine as well as other cationic substrates (e.g. ______,_________,_________) and competitive inhibitors.

The esteratic subsite, where acetylcholine is hydrolyzed to acetate and choline, contains the catalytic triad of three amino acids: ________,__________, and __________

A

positive quaternary

edrophonium, N-methyl acridinium

serine 203, histidine 447, and glutamate 334.

81
Q

• Apart from the true cholinesterase(_______), there is the non-specific ___________esterase, also known as ____________esterase. It is found in the __________ and elsewhere in the body to metabolize ingested _________.

A

AChE

butyrylcholin

pseudocholin

plasma; esters

82
Q

Differences Between Acetylcholinesterase (A) and Pseudocholinesterase (B)

  1. A is found distributed in _______,_______, and ________ , while B is in the _______,_______,________, and _____
  2. A hydrolyses ACh very ______ but methacholine _______. It has ______ action on benzoylcholine and butyrylcholine.

B, on the other hand, hydrolysis ACh _________ , and it’s very ______ on benzoylcholine and butyrylcholine. It has _____ effect on methacholine.

A

all cholinergic sites, RBC, and grey matter; plasma, liver, intestine, and white matter.

fast; slowly; no

slowly; active; no

83
Q

Differences Between Acetylcholinesterase (A) and Pseudocholinesterase (B)

(A) is more sensitive to the inhibitory action of ____________ , while (B) is more sensitive to the ____________.

(A) terminates ________ , while B hydrolyzes ____________

A

physostigmine; organophosphates

ACh action; ingested esters.

84
Q

There are two broad classes of cholinergic receptors: __________ and ___________.

A

nicotinic

muscarinic

85
Q

nicotinic ACh receptors are located at the _______,________, and sparsely in the ———.

A

NMJ, autonomic ganglia

CNS

86
Q

The NMJ nicotinic ACh receptor consists of ______ polypeptide subunits:

List them

A

five

two α subunits and one each of β, δ, and γ.

87
Q

Nicotinic VS muscarinic ACh receptors

Binds??
Blocked by???
Linked to ??

A

Nicotine; muscarine

Curare(tubocurarine) ; atropine

Ionic channels; 2nd messenger systems through G proteins

88
Q

Nicotinic VS muscarinic ACh receptors

Duration and speed of response
Pre or post synaptic?
Mediates ???

A

Brief and fast; slow and prolonged

Post; pre and post

Excitation; inhibition and excitation

89
Q

NMJ nicotinic ACh receptor

• A _____-shaped internal ion channel is surrounded by the five subunits.
•The binding surface of the receptor appears to be primarily on the ____ subunits, near the (inner or outer?) surface of the molecule.
• The subunits contain recognition sites for agonists, reversible antagonists, and α-toxins.

A

funnel; α

Outer

90
Q

Whereas the NMJ nicotinic receptor is composed of _______ different species of subunit (__________), the neuronal nicotinic receptor also is composed of only ______ subunit types (———- and ______ ).

A

four; 2 α, β, γ, δ

two

2 α and 3 β

91
Q

Muscarinic receptors, classified as ______________________ receptors (GPCR) ( __________ Receptors), are located at parasympathetic autonomically innervated visceral organs, on the sweat glands and piloerector muscles, and both post-synaptically and pre-synaptically in the CNS

A

G protein-coupled

Metabotropic

92
Q

The muscarinic receptor is composed of a single polypeptide.

• Seven regions of the polypeptide are made up of ________ amino acids arranged in an __________.

• Because each of these regions of the protein is markedly hydro_______, they span the cell membrane ______ times .

A

20-25 ; α helix

phobic; seven

93
Q

ACh has (inhibitory or excitatory?) actions at the neuromuscular junction, at the autonomic ganglion, at certain glandular tissues, and in the CNS. It has (inhibitory or excitatory?) actions at certain smooth muscles and at cardiac muscles.

A

excitatory

inhibitory

94
Q

G protein is made up of the _______ subunits ___________.

A

three

α, β and γ.

95
Q

In response to the altered conformation of the muscarinic receptor, the alpha subunit of the G protein releases bound __________________ and simultaneously binds _______________

A

guanosine diphosphate (GDP)

guanosine triphosphate (GTP).

House Pharmacology (50 decks)

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