ACETYLCHOLINE: SYNTHESIS, STORAGE, RELEASE, FATE & METABOLISM Flashcards
Function of Ach in the somatic nervous systems
responsible for all motor transmission in vertebrates
Function of Ach In the ANS
mediates parasympathetic actions of the autonomic nervous system
What are the sites of release for Ach
•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
Sites of release of Noradrenaline
•Most sympathetic post ganglionic terminals
•Adrenal medulla
•CNS
What’s the effect of sympathetic on the heart, blood vessels, lungs, digestive tracts, urinary bladder, eye, liver, adipose cells
•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
What’s the effect of parasympathetic innervation on heart, blood vessels, lungs, digestive tracts, urinary bladder, eye, liver, adipose cells
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
Effect of sympathetic stimulation on exocrine pancreas, sweat glands, salivary glands, endocrine pancreas, adrenal medulla, genitalia and brain activity
•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
Effect of parasympathetic stimulation on exocrine pancreas, sweat glands, salivary glands, endocrine pancreas, adrenal medulla, genitalia and brain activity
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
What are the Exceptions to general rule of dual reciprocal innervation by the two branches of autonomic nervous system
– 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
Function of Ach in the forebrain
Forebrain: arousal and attention
– Learning and memory?
– Alzheimer Disease
Effect of Ach on parabrachial nucleus
– Continue to fire during REM
– # Cells correlate with REM sleepe
What’s the function of Ach in the ANS
Arousal and attention (forebrain)
REM sleep (parabrachial nucleus)
Reward and addiction
Pain and other sensory input
Function of Ach in the PNS
• 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
What does regulated release of Ach cause
Regulated release of Ach causes muscle depolarization: mEPP or EPSP
– Contraction of muscle
Explain the synthesis of Ach
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
Explain the degradation of Ach
Ach Is broken down to acetate and choline with the help of acetylcholinesterase
The choline is taken up again
What inhibits the action of cholineacetyl transferase
mercurials
What inhibits acetylcholinesterase
Physostigmine reversibly
inhibited by nerve agents, sarin irreversibly
What is the Ach equilibrium
• Ach levels are extremely stable over a wide range of neural activity
What does availability of choline to the the do to the reaction (synthesis of Ach)
– Availability of choline (CHT) drives rxn to the rightm
What does a decrease in Ach do to the equilibrium
– Decrease in Ach will cause shift in equilibrium (no substrate for reverse rxn)
What does the action potential of Ach do at the presynaptic terminal
It depolarizes the membrane
What must be present for Ach to be released and have any effect
Ca2+
Other than Ca2+, what other factors affect Ach release
• Trophic factors
• NGF exerts rapid short term effects on Ach
synthesis and release
• Estrogen (other hormones?)
Functions of acetylcholinesterase
• 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
Is acetylcholinesterase a marker for cholinergic cells
No
What does acetylcholinesterase do to receptor signaling
Limits receptor signaling events/duration
What are inhibitors of acetylcholinesterase
– Alzheimer disease (Aricept)
– Glaucoma, myasthenia gravis
– Bioterrorism
What vessels are not innervated
Arteries and capillaries
What disease are anticholinestearses used to treat
Alzheimer’s disease
Glaucoma, my Esther’s gra is
Bioterrorism
What is peculiar about the adrenal medulla
It only gets pregamglionuc innervation
By Ach
The enterochromaffin cells/neurochromocytes embedded in the adrenal medulla is the modifies post ganglionic neuron
How is Ach stored
Stored in vesicles and shuttled in by VAT
Describe the release of Ach
• 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
What’s the action of Ach after its released
Binds to cholinergic receptor on the post ganglionic neuron
What drug blocks the synthesis of Ach
Hemicholinium blocks the choline transporter
What drug blocks the storage of Ach
Vesamicol prevents Ach from getting into the vesicle by VAT
What drug blocks the release of Ach
Botulinum toxins
What drugs influence the action of Ach
Cholinergic agonist and antagonist
What inhibits the metabolism of Ach
Anticholinesterase
