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Pharmacology GPP > ACETYLCHOLINE: SYNTHESIS, STORAGE, RELEASE, FATE & METABOLISM > Flashcards

ACETYLCHOLINE: SYNTHESIS, STORAGE, RELEASE, FATE & METABOLISM Flashcards

1
Q

Function of Ach in the somatic nervous systems

A

responsible for all motor transmission in vertebrates

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2
Q

Function of Ach In the ANS

A

mediates parasympathetic actions of the autonomic nervous system

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3
Q

What are the sites of release for Ach

A

•All pre ganglionic terminals for ANS
•All post ganglionic terminals for parasympathetic
•Sympathetic Post ganglionic terminals for sweat glands and some blood vessels in skeletal muscle
•Terminals of efferent neurons supplying skeletal neurons
•CNS

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4
Q

Sites of release of Noradrenaline

A

•Most sympathetic post ganglionic terminals
•Adrenal medulla
•CNS

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5
Q

What’s the effect of sympathetic on the heart, blood vessels, lungs, digestive tracts, urinary bladder, eye, liver, adipose cells

A

•Increase rate of heart
•Constricts blood vessels
•Dilate bronchioles and inhibit yeamucus secretion
•Decrease motility of GIT, contract sphincters, inhibit digestive secretion
•Relaxation of urinary bladder
•Dilation of pupil
Adjustment of vision for far sight
•Glycogenolysis
•Lipolysis

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6
Q

What’s the effect of parasympathetic innervation on heart, blood vessels, lungs, digestive tracts, urinary bladder, eye, liver, adipose cells

A

Decrease heart rate
Dilate blood vessels
Constrict bronchioles and stimulate mucus secretion
Stimulate gastric motility and secretions, relax sphincters
Constriction of bladder
Adjustment of vision for near vision
No effect on liver and adipose cells

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7
Q

Effect of sympathetic stimulation on exocrine pancreas, sweat glands, salivary glands, endocrine pancreas, adrenal medulla, genitalia and brain activity

A

•Inhibition of exocrine secretions
•Stimulation of sweat glands
•Stimulation of small thick saliva
•Inhibition of insulin, stimulation of glucagon stimulation
•Secretion of epinephrine and norepinephrine
•Ejaculation and orgasmic contraction
•Increased alertness

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8
Q

Effect of parasympathetic stimulation on exocrine pancreas, sweat glands, salivary glands, endocrine pancreas, adrenal medulla, genitalia and brain activity

A

Stimulates exocrine stimulation
Inhibit sweat secretion
Production of large watery saliva filled with enzymes
Stimulation of insulin and glucagon
Erection of genetalia
No effect on brain activity

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9
Q

What are the Exceptions to general rule of dual reciprocal innervation by the two branches of autonomic nervous system

A

– Most arterioles and veins receive only sympathetic nerve fibers (arteries and capillaries are not innervated)
– Most sweat glands are innervated only by sympathetic nerves
– Salivary glands are innervated by both ANS divisions but activity is not antagonistic – both stimulate salivary secretion
- Adrenal medulla are innervated by preganglionic only

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10
Q

Function of Ach in the forebrain

A

Forebrain: arousal and attention
– Learning and memory?
– Alzheimer Disease

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11
Q

Effect of Ach on parabrachial nucleus

A

– Continue to fire during REM
– # Cells correlate with REM sleepe

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12
Q

What’s the function of Ach in the ANS

A

Arousal and attention (forebrain)
REM sleep (parabrachial nucleus)
Reward and addiction
Pain and other sensory input

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13
Q

Function of Ach in the PNS

A

• Vasculature (endothelial cells) – Release of endothelium-derived relaxing factor (NO) and vasodilation
• Eye iris (pupillae sphincter muscle) – Contraction and miosis
• Ciliary muscle – Contraction and accommodation of lens to near vision
• Salivary and lacrimal glands – Secretion (thin and watery)
• Bronchi – Constriction, increased secretions
• Heart – Bradycardia, decreased conduction (AV block at high doses), negative inotropic acti

• GIT – Increased tone, increased secretions, relaxation at sphincters
• Urinary bladder – Contraction of detrusor muscle, relaxation at sphincters
• Sweat glands – Diaphoresis
• Reproductive tract, male – Erection
• Uterus – Variable, depending on hormonal influence

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14
Q

What does regulated release of Ach cause

A

Regulated release of Ach causes muscle depolarization: mEPP or EPSP
– Contraction of muscle

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15
Q

Explain the synthesis of Ach

A

Pyruvate is converted to AcetylCoA with the help of PDH complex (FAD, Lipoamide, TPP)
Acetyl CoA donates its acetyl group that combines with choline with the help of choline acetyl transferase

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16
Q

Explain the degradation of Ach

A

Ach Is broken down to acetate and choline with the help of acetylcholinesterase
The choline is taken up again

17
Q

What inhibits the action of cholineacetyl transferase

A

mercurials

18
Q

What inhibits acetylcholinesterase

A

Physostigmine reversibly

inhibited by nerve agents, sarin irreversibly

19
Q

What is the Ach equilibrium

A

• Ach levels are extremely stable over a wide range of neural activity

20
Q

What does availability of choline to the the do to the reaction (synthesis of Ach)

A

– Availability of choline (CHT) drives rxn to the rightm

21
Q

What does a decrease in Ach do to the equilibrium

A

– Decrease in Ach will cause shift in equilibrium (no substrate for reverse rxn)

22
Q

What does the action potential of Ach do at the presynaptic terminal

A

It depolarizes the membrane

23
Q

What must be present for Ach to be released and have any effect

A

Ca2+

24
Q

Other than Ca2+, what other factors affect Ach release

A

• Trophic factors
• NGF exerts rapid short term effects on Ach
synthesis and release
• Estrogen (other hormones?)

25
Q

Functions of acetylcholinesterase

A

• Hydrolysis and deactivation of acetylcholine
• Prevents acetylcholine reactivating receptor
• Critical for recycling choline
• Limits receptor signaling events/duration
• Found in extracellular space, synaptic cleft: not a marker of cholinergic cells

26
Q

Is acetylcholinesterase a marker for cholinergic cells

A

No

27
Q

What does acetylcholinesterase do to receptor signaling

A

Limits receptor signaling events/duration

28
Q

What are inhibitors of acetylcholinesterase

A

– Alzheimer disease (Aricept)
– Glaucoma, myasthenia gravis
– Bioterrorism

29
Q

What vessels are not innervated

A

Arteries and capillaries

30
Q

What disease are anticholinestearses used to treat

A

Alzheimer’s disease
Glaucoma, my Esther’s gra is
Bioterrorism

31
Q

What is peculiar about the adrenal medulla

A

It only gets pregamglionuc innervation
By Ach

The enterochromaffin cells/neurochromocytes embedded in the adrenal medulla is the modifies post ganglionic neuron

32
Q

How is Ach stored

A

Stored in vesicles and shuttled in by VAT

33
Q

Describe the release of Ach

A

• AP goes through the membrane
• Once AP gets to the axon, it opens up Ca2+ gated channels and causes an influx
• The excess Ca2+ pulls the vesicle to the end of the membrane
The vesicle fuses to the membrane, exocytosis occurs and Ach is released

34
Q

What’s the action of Ach after its released

A

Binds to cholinergic receptor on the post ganglionic neuron

35
Q

What drug blocks the synthesis of Ach

A

Hemicholinium blocks the choline transporter

36
Q

What drug blocks the storage of Ach

A

Vesamicol prevents Ach from getting into the vesicle by VAT

37
Q

What drug blocks the release of Ach

A

Botulinum toxins

38
Q

What drugs influence the action of Ach

A

Cholinergic agonist and antagonist

39
Q

What inhibits the metabolism of Ach

A

Anticholinesterase

Pharmacology GPP (5 decks)

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