Chapter 7 on acetylcholine provides a comprehensive overview of the role and mechanisms of this essential neurotransmitter. It discusses the synthesis of acetylcholine (ACh) by the enzyme choline acetyltransferase from choline and acetyl coenzyme A and how its production is influenced by precursor ...
TEST BANK For Psychopharmacology: Drugs, the Brain, and Behavior, 4th Edition By Meyer Nursing, Verified Chapters 1 - 20, Complete Newest Version
TEST BANK For Psychopharmacology: Drugs, the Brain, and Behavior, 4th Edition By Meyer Nursing, Verified Chapters 1 - 20, Complete
TEST BANK For Psychopharmacology: Drugs, the Brain, and Behavior, 4th Edition By Meyer Nursing, Verified Chapters 1 - 20, Complete Newest Version
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Acetylcholine
Acetylcholine Synthesis, Release, and Inactivation
- Acetylcholine (ACh) is a crucial neurotransmitter in the peripheral nervous system (PNS),
operating at neuromuscular junctions and autonomic nervous system synapses.
- While ACh is synthesized by a limited number of neurons in the brain, these neurons are
pivotal for various behavioral functions.
- Understanding the production, release, and inactivation of ACh is vital due to the risks
associated with both excessive and insu cient levels of this neurotransmitter.
- Various agents modulate ACh levels in the body, either increasing or limiting its availability to
regulate physiological and behavioral processes.
Acetylcholine synthesis is catalyzed by the enzyme choline acetyltransferase
- Acetylcholine (ACh) is synthesized in a single step from choline and acetyl coenzyme A
(acetyl CoA).
- Choline is sourced from dietary fat or produced in the liver, while acetyl CoA is generated
within cells through sugar and fat metabolism.
- Choline acetyltransferase (ChAT) catalyzes the synthesis of ACh by transferring the acetyl
group from acetyl CoA to choline.
- ChAT is speci c to neurons that utilize ACh as a neurotransmitter, allowing for their
identi cation through ChAT staining.
- The rate of ACh synthesis is in uenced by the availability of precursors and neuronal ring
rate.
- Despite understanding regulatory mechanisms, pharmacological agents targeting ACh
synthesis have been challenging to develop.
- Boosting brain ACh levels with choline was explored for Alzheimer’s disease but proved
ine ective and caused undesirable side e ects like a shy odor due to peripheral metabolism
of choline.
Many di erent drugs and toxins can alter acetylcholine storage and release
- Cholinergic neurons store acetylcholine (ACh) in synaptic vesicles within axon terminals for
release during neuronal activity.
- Vesicular ACh transporter (VAChT) is responsible for loading ACh into synaptic vesicles, and
its inhibition by vesamicol decreases ACh storage in vesicles.
- Vesamicol treatment increases cytoplasmic ACh levels as ACh molecules that would have
been transported into vesicles remain in the cytoplasm.
- Reduced ACh release occurs in the presence of vesamicol since synaptic vesicles, the
primary source of ACh release during neuronal ring, have lower ACh content.
- Despite vesamicol treatment, empty synaptic vesicles continue to undergo exocytosis and
recycling when cholinergic neurons are activated, indicating a lack of feedback mechanisms to
prevent release of vesicles with low or no neurotransmitter content.
- Black widow spider venom induces massive ACh release at synapses in the peripheral
nervous system, leading to symptoms like muscle pain, tremors, nausea, salivation, and
sweating.
- Botulism toxins inhibit ACh release, causing muscular paralysis, which can be fatal. However,
carefully administered localized botulinum toxin injections have medical and cosmetic
applications.
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Acetylcholinesterase is responsible for acetylcholine breakdown
- Acetylcholine (ACh) levels are regulated by acetylcholinesterase (AChE), which breaks down
ACh into choline and acetic acid.
- AChE exists as a tetramer formed by four subunits, with the majority tethered to the cell
membrane for rapid ACh breakdown.
- A unique form of AChE, A12, is found at neuromuscular junctions, ensuring precise
transmission and rapid muscle relaxation.
- Recycled choline plays a critical role in sustaining ACh synthesis, as shown by knockout
studies of the choline transporter in mice.
- Drugs that block AChE increase postsynaptic e ects of ACh, with reversible inhibitors used to
treat age-related dementia, such as donepezil, rivastigmine, and galantamine.
- Natural reversible AChE inhibitors like physostigmine have medical applications but can be
highly toxic, with symptoms of poisoning including mental confusion and convulsions.
- Irreversible AChE inhibitors, like organophosphorus compounds, cause nearly irreversible
inhibition of AChE activity and are used as insecticides or, in more toxic forms, as nerve gases.
- Nerve gases like sarin and soman rapidly accumulate ACh, leading to symptoms such as
profuse sweating, convulsions, and eventually death due to muscle paralysis.
- During con icts, reversible AChE inhibitors like pyridostigmine are used prophylactically to
protect against nerve gas poisoning, but excessive exposure may contribute to long-term
health issues like Gulf War illness, a complex neuroimmune disorder a icting some veterans.
Several neuromuscular disorders are associated with abnormal cholinergic
functioning at the neuromuscular junction
- Myasthenia gravis is an autoimmune disorder where antibodies attack skeletal muscle
cholinergic receptors, leading to muscle weakness and fatigue.
- Loss of receptor function reduces muscle sensitivity to ACh, causing symptoms like
weakness, fatigue, speech di culties, labored breathing, and drooping eyelids.
- Diagnosis of myasthenia gravis can be challenging due to shared symptoms with other
neuromuscular disorders, but treatment involves administering AChE inhibitors like
pyridostigmine or neostigmine to enhance the e ectiveness of remaining cholinergic receptors.
- Congenital neuromuscular disorders, termed myasthenic syndromes, can result from
mutations in genes encoding ChAT or AChE, leading to insu cient ACh release or persistent
ACh activity at neuromuscular junctions.
- Symptoms of myasthenic syndromes, which appear in infancy, include muscle weakness,
respiratory distress, episodes of apnea, and drooping eyelids.
- Treatment for myasthenic syndromes caused by de cient ChAT activity involves AChE
inhibitors like pyridostigmine, but there are currently no e ective remedies for syndromes
caused by AChE gene mutations.
Organization and Function of the Cholinergic System
- Acetylcholine (ACh) serves as a neurotransmitter at the neuromuscular junction and within the
autonomic nervous system, where it was initially identi ed as a neurotransmitter in the
peripheral nervous system (PNS).
- Cholinergic cell bodies and synapses are located in both the PNS and CNS.
- The receptor subtypes for ACh will be described, along with some of the primary behavioral
and physiological functions of this neurotransmitter in the subsequent sections.
Cholinergic neurons play a key role in the functioning of both the peripheral and
central nervous systems
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