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Questions and Answers
What is the role of the vesicle-associated transporter (VAT) in neurotransmitter transport?
What is the role of the vesicle-associated transporter (VAT) in neurotransmitter transport?
What triggers the exocytosis of neurotransmitter vesicles at the nerve terminal?
What triggers the exocytosis of neurotransmitter vesicles at the nerve terminal?
Which enzyme is responsible for converting tyrosine to Dopa in adrenergic transmission?
Which enzyme is responsible for converting tyrosine to Dopa in adrenergic transmission?
Which statement about dopamine in adrenergic transmission is true?
Which statement about dopamine in adrenergic transmission is true?
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What role does the vesicular monoamine transporter (VMAT) play in adrenergic transmission?
What role does the vesicular monoamine transporter (VMAT) play in adrenergic transmission?
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What is the main precursor for the synthesis of acetylcholine (ACh)?
What is the main precursor for the synthesis of acetylcholine (ACh)?
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Which enzyme is responsible for synthesizing acetylcholine from acetyl-CoA and choline?
Which enzyme is responsible for synthesizing acetylcholine from acetyl-CoA and choline?
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How is the action of neurotransmitters typically terminated in the synapse?
How is the action of neurotransmitters typically terminated in the synapse?
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Where are most neurotransmitters synthesized in the autonomic nervous system?
Where are most neurotransmitters synthesized in the autonomic nervous system?
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What type of neurotransmitter is ATP considered in the context of the autonomic nervous system?
What type of neurotransmitter is ATP considered in the context of the autonomic nervous system?
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Which neurotransmitter is NOT included when discussing the main autonomic transmitters?
Which neurotransmitter is NOT included when discussing the main autonomic transmitters?
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In the context of neurotransmission, what do drugs specifically target?
In the context of neurotransmission, what do drugs specifically target?
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What kind of transport mechanism is used for choline to enter the nerve terminal?
What kind of transport mechanism is used for choline to enter the nerve terminal?
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Which neurotransmitter is classified as a NANC mediator in the sympathetic nervous system?
Which neurotransmitter is classified as a NANC mediator in the sympathetic nervous system?
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What is the role of hemicholinium in cholinergic neurotransmission?
What is the role of hemicholinium in cholinergic neurotransmission?
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Which of the following is NOT considered a NANC neurotransmitter?
Which of the following is NOT considered a NANC neurotransmitter?
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What does vesamicol block in cholinergic neurotransmission?
What does vesamicol block in cholinergic neurotransmission?
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Which step of neurotransmission is primarily affected when drugs interfere with the release of neurotransmitters?
Which step of neurotransmission is primarily affected when drugs interfere with the release of neurotransmitters?
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Which of the following is a common effect of drugs on neurotransmission?
Which of the following is a common effect of drugs on neurotransmission?
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Which neurotransmitter is not classified under the category of NANC mediators of the ANS?
Which neurotransmitter is not classified under the category of NANC mediators of the ANS?
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What is the primary function of nitric oxide as a NANC neurotransmitter?
What is the primary function of nitric oxide as a NANC neurotransmitter?
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Which drug can inhibit the breakdown of norepinephrine?
Which drug can inhibit the breakdown of norepinephrine?
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What is the effect of tricyclic antidepressants on norepinephrine?
What is the effect of tricyclic antidepressants on norepinephrine?
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What is the role of MAO inhibitors like selegiline in neurotransmission?
What is the role of MAO inhibitors like selegiline in neurotransmission?
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Which neurotransmitter is also known as noradrenaline?
Which neurotransmitter is also known as noradrenaline?
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Which of the following is a non-adrenergic, non-cholinergic neurotransmitter?
Which of the following is a non-adrenergic, non-cholinergic neurotransmitter?
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What is the role of metyrosine in the synthesis of neurotransmitters?
What is the role of metyrosine in the synthesis of neurotransmitters?
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How does reserpine affect neurotransmitter storage?
How does reserpine affect neurotransmitter storage?
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Which drug inhibits the release of norepinephrine into the synapse?
Which drug inhibits the release of norepinephrine into the synapse?
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What class of drug is salbutamol and what is its primary action?
What class of drug is salbutamol and what is its primary action?
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What effect does guanethidine have in the context of adrenergic neurotransmission?
What effect does guanethidine have in the context of adrenergic neurotransmission?
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Which statement correctly describes the function of acetylcholinesterase?
Which statement correctly describes the function of acetylcholinesterase?
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Which of the following is NOT a site of drug action in adrenergic neurotransmission?
Which of the following is NOT a site of drug action in adrenergic neurotransmission?
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The role of presynaptic receptors at muscarinic cholinergic junctions is to:
The role of presynaptic receptors at muscarinic cholinergic junctions is to:
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What effect do tricyclic antidepressants have on norepinephrine levels in the synapse?
What effect do tricyclic antidepressants have on norepinephrine levels in the synapse?
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Which drug class is capable of inhibiting the breakdown of norepinephrine in the body?
Which drug class is capable of inhibiting the breakdown of norepinephrine in the body?
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What is the primary role of MAO inhibitors like selegiline in neurotransmission?
What is the primary role of MAO inhibitors like selegiline in neurotransmission?
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What neurotransmitter is also known as norepinephrine?
What neurotransmitter is also known as norepinephrine?
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Which of the following statements about COMT-inhibitors is true?
Which of the following statements about COMT-inhibitors is true?
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What is the significance of the influx of Ca²⁺ at the nerve terminal during neurotransmission?
What is the significance of the influx of Ca²⁺ at the nerve terminal during neurotransmission?
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Which enzyme is responsible for converting Dopamine to Noradrenaline (NA) within the vesicle?
Which enzyme is responsible for converting Dopamine to Noradrenaline (NA) within the vesicle?
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How is Tyrosine transported into the presynaptic nerve terminal during adrenergic transmission?
How is Tyrosine transported into the presynaptic nerve terminal during adrenergic transmission?
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What role does the vesicular monoamine transporter (VMAT) perform in adrenergic neurotransmission?
What role does the vesicular monoamine transporter (VMAT) perform in adrenergic neurotransmission?
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What initiates the process of neurotransmitter release at the nerve terminal?
What initiates the process of neurotransmitter release at the nerve terminal?
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Which enzyme is responsible for the conversion of Dopa to Dopamine in the synthesis of catecholamines?
Which enzyme is responsible for the conversion of Dopa to Dopamine in the synthesis of catecholamines?
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What is the primary urinary metabolite produced from noradrenaline metabolism?
What is the primary urinary metabolite produced from noradrenaline metabolism?
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Which enzyme primarily catalyzes the main oxidative pathway in the metabolism of noradrenaline?
Which enzyme primarily catalyzes the main oxidative pathway in the metabolism of noradrenaline?
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Which compound inhibits the rate-limiting step in catecholamine synthesis?
Which compound inhibits the rate-limiting step in catecholamine synthesis?
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Which of the following is a less abundant metabolite produced in noradrenaline metabolism?
Which of the following is a less abundant metabolite produced in noradrenaline metabolism?
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What is the initial step in the synthesis of acetylcholine (ACh) in the cholinergic transmission process?
What is the initial step in the synthesis of acetylcholine (ACh) in the cholinergic transmission process?
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How does the conjugation of MHPG before excretion relate to noradrenaline release?
How does the conjugation of MHPG before excretion relate to noradrenaline release?
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What is noradrenaline also known as?
What is noradrenaline also known as?
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Which of the following best describes how neurotransmitter action is terminated?
Which of the following best describes how neurotransmitter action is terminated?
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Which of the following enzymes is involved in the metabolism of catecholamines but is not a rate-limiting step?
Which of the following enzymes is involved in the metabolism of catecholamines but is not a rate-limiting step?
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What characterizes neurotransmitters synthesized in the nerve terminals of the autonomic nervous system?
What characterizes neurotransmitters synthesized in the nerve terminals of the autonomic nervous system?
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What role do drugs typically play in neurochemical transmission?
What role do drugs typically play in neurochemical transmission?
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Which of the following is a non-adrenergic, non-cholinergic (NANC) neurotransmitter involved in the autonomic nervous system?
Which of the following is a non-adrenergic, non-cholinergic (NANC) neurotransmitter involved in the autonomic nervous system?
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What is the primary function of the enzyme choline acetyltransferase (ChAT)?
What is the primary function of the enzyme choline acetyltransferase (ChAT)?
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What is the effect of ATP as a NANC neurotransmitter in the autonomic nervous system?
What is the effect of ATP as a NANC neurotransmitter in the autonomic nervous system?
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Which component is fundamental to the process of storing neurotransmitters in the autonomic nervous system?
Which component is fundamental to the process of storing neurotransmitters in the autonomic nervous system?
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What effect does botulinum toxin have on acetylcholine release at the nerve terminal?
What effect does botulinum toxin have on acetylcholine release at the nerve terminal?
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How do acetylcholinesterase inhibitors like pyridostigmine affect acetylcholine levels?
How do acetylcholinesterase inhibitors like pyridostigmine affect acetylcholine levels?
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What is the role of presynaptic nicotinic receptors at the cholinergic synapse?
What is the role of presynaptic nicotinic receptors at the cholinergic synapse?
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What is the primary effect of using agonist drugs at postsynaptic nicotinic receptors?
What is the primary effect of using agonist drugs at postsynaptic nicotinic receptors?
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What occurs to acetylcholine levels when acetylcholinesterase is inhibited?
What occurs to acetylcholine levels when acetylcholinesterase is inhibited?
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What type of receptors are present at muscarinic cholinergic junctions?
What type of receptors are present at muscarinic cholinergic junctions?
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Which of the following statements about acetylcholine leakage is true under normal conditions?
Which of the following statements about acetylcholine leakage is true under normal conditions?
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What is the primary mechanism of action for atropine in the cholinergic system?
What is the primary mechanism of action for atropine in the cholinergic system?
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What is the role of the vesicular monoamine transporter (VMAT) in the process of adrenergic transmission?
What is the role of the vesicular monoamine transporter (VMAT) in the process of adrenergic transmission?
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Which of the following correctly describes the influx of Ca²⁺ at the nerve terminal?
Which of the following correctly describes the influx of Ca²⁺ at the nerve terminal?
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Which enzyme is specifically responsible for converting Dopamine into Noradrenaline (NA) within the vesicle?
Which enzyme is specifically responsible for converting Dopamine into Noradrenaline (NA) within the vesicle?
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What role does tyrosine hydroxylase play in adrenergic transmission?
What role does tyrosine hydroxylase play in adrenergic transmission?
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Which transport mechanism is utilized for the uptake of Tyrosine into the presynaptic nerve terminal?
Which transport mechanism is utilized for the uptake of Tyrosine into the presynaptic nerve terminal?
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What effect do tricyclic antidepressants have on norepinephrine levels in the synapse?
What effect do tricyclic antidepressants have on norepinephrine levels in the synapse?
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Which drug class can inhibit the breakdown of norepinephrine?
Which drug class can inhibit the breakdown of norepinephrine?
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Which of the following neurotransmitters is predominantly associated with the parasympathetic nervous system as a NANC mediator?
Which of the following neurotransmitters is predominantly associated with the parasympathetic nervous system as a NANC mediator?
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Which neurotransmitter is also known as noradrenaline?
Which neurotransmitter is also known as noradrenaline?
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Which step of neurotransmission involves the blockage of the choline transporter by hemicholinium?
Which step of neurotransmission involves the blockage of the choline transporter by hemicholinium?
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What is the role of COMT inhibitors in neurotransmission?
What is the role of COMT inhibitors in neurotransmission?
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Which compound acts as a neurotransmitter that is non-adrenergic and non-cholinergic (NANC)?
Which compound acts as a neurotransmitter that is non-adrenergic and non-cholinergic (NANC)?
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Vesamicol primarily inhibits neurotransmission by acting on which aspect?
Vesamicol primarily inhibits neurotransmission by acting on which aspect?
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Which of the following is NOT recognized as a major NANC mediator in the sympathetic nervous system?
Which of the following is NOT recognized as a major NANC mediator in the sympathetic nervous system?
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Which neurotransmitter is associated with inhibitory effects and is classified among the NANC neurotransmitters?
Which neurotransmitter is associated with inhibitory effects and is classified among the NANC neurotransmitters?
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What is the main mechanism through which drugs can disrupt neurotransmission?
What is the main mechanism through which drugs can disrupt neurotransmission?
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Which neurotransmitter plays a significant role in both NANC mediation and as a neurotransmitter in the central nervous system?
Which neurotransmitter plays a significant role in both NANC mediation and as a neurotransmitter in the central nervous system?
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What is one of the critical actions of ATP as a neurotransmitter in the sympathetic nervous system?
What is one of the critical actions of ATP as a neurotransmitter in the sympathetic nervous system?
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What is the main urinary metabolite produced from the oxidative metabolism of noradrenaline?
What is the main urinary metabolite produced from the oxidative metabolism of noradrenaline?
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Which enzyme is primarily responsible for converting noradrenaline into its metabolites in the brain?
Which enzyme is primarily responsible for converting noradrenaline into its metabolites in the brain?
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What is inhibited by the drug metyrosine during catecholamine synthesis?
What is inhibited by the drug metyrosine during catecholamine synthesis?
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Which of the following statements accurately reflects the role of aldehyde reductase (AR) in noradrenaline metabolism?
Which of the following statements accurately reflects the role of aldehyde reductase (AR) in noradrenaline metabolism?
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Which neurotransmitter is chemically modified to form noradrenaline during its synthesis?
Which neurotransmitter is chemically modified to form noradrenaline during its synthesis?
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In the context of noradrenaline metabolism, what does MHPG sulfate excretion indicate?
In the context of noradrenaline metabolism, what does MHPG sulfate excretion indicate?
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What role does catechol-O-methyltransferase (COMT) play in the metabolism of catecholamines?
What role does catechol-O-methyltransferase (COMT) play in the metabolism of catecholamines?
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Which enzyme indicates the primary pathway leading to the formation of the main urinary metabolite from noradrenaline?
Which enzyme indicates the primary pathway leading to the formation of the main urinary metabolite from noradrenaline?
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What is the primary mechanism of action for the drug bretylium in adrenergic neurotransmission?
What is the primary mechanism of action for the drug bretylium in adrenergic neurotransmission?
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Which of the following drugs acts as an antagonist at specific adrenergic receptor subtypes?
Which of the following drugs acts as an antagonist at specific adrenergic receptor subtypes?
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What is the impact of resperine on neurotransmitter storage?
What is the impact of resperine on neurotransmitter storage?
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How do agonists like salbutamol function at the adrenergic synapse?
How do agonists like salbutamol function at the adrenergic synapse?
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Which process is primarily inhibited by guanethidine in the context of adrenergic neurotransmission?
Which process is primarily inhibited by guanethidine in the context of adrenergic neurotransmission?
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What is the biological consequence of using metyrosine in adrenergic neurotransmission?
What is the biological consequence of using metyrosine in adrenergic neurotransmission?
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What role do postsynaptic muscarinic receptors play in adrenergic neurotransmission?
What role do postsynaptic muscarinic receptors play in adrenergic neurotransmission?
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What is the primary site of action for drugs designed to inhibit vesicular storage of neurotransmitters?
What is the primary site of action for drugs designed to inhibit vesicular storage of neurotransmitters?
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Study Notes
Autonomic Nervous System Transmission
- Autonomic neurotransmission involves the synthesis, storage, release, and termination of neurotransmitters in response to nerve stimulation.
- Most neurotransmitters are synthesized in nerve terminals, stored in membrane-bound vesicles, and released into the synapse upon nerve stimulation.
- Neurotransmitter action is terminated by metabolism or reuptake from the synapse.
- Drugs often exert effects on specific steps in the neurotransmission process.
Cholinergic Transmission
- The precursor for acetylcholine (ACh) is choline, transported into nerve terminals by the choline transporter (CHT).
- ACh is synthesized in the cytoplasm using acetyl-CoA and choline, catalyzed by the enzyme choline acetyltransferase (ChAT).
- ACh is transported from the cytoplasm into vesicles by a vesicle-associated transporter (VAT).
- Nerve stimulation triggers an influx of calcium ions (Ca²⁺) through voltage-gated Ca²⁺ channels, leading to vesicle exocytosis and ACh release into the synapse.
Adrenergic Transmission
- Tyrosine is transported into the presynaptic nerve terminal by a sodium-dependent carrier.
- Tyrosine is converted to Dopa by the enzyme tyrosine hydroxylase.
- Dopa is converted to Dopamine by the enzyme dopa decarboxylase.
- Dopamine is transported into vesicles by the vesicular monoamine transporter (VMAT).
- Inside the vesicle, Dopamine is converted to Noradrenaline (NA) by the enzyme dopamine-β-hydroxylase.
Non-Adrenergic Non-Cholinergic (NANC) Mediators
- NANC neurotransmitters are those other than NA and ACh.
- Major NANC mediators in the autonomic nervous system include:
- Nitric oxide and vasoactive intestinal peptide (VIP) in the parasympathetic nervous system.
- ATP and neuropeptide Y in the sympathetic nervous system.
- Other NANC mediators include 5-hydroxytryptamine (serotonin), GABA, and dopamine.
Drug Effects on Neurotransmission
- Drugs can interfere with neurotransmission at various stages:
- Synthesis of neurotransmitters
- Storage of neurotransmitters in vesicles
- Release of neurotransmitters into the synapse
- Interaction of neurotransmitters with post-synaptic receptors
- Termination of neurotransmitter action
Drug Effects on Cholinergic Neurotransmission
- Hemicholinium blocks the choline transporter, preventing the transport of choline into the nerve terminal, thereby inhibiting ACh synthesis.
- Vesamicol blocks the vesicle-associated transporter (VAT), preventing ACh from being transported from the cytoplasm into the vesicle.
Drug Effects on Adrenergic Neurotransmission
- Metyrosine inhibits the conversion of tyrosine to Dopa, disrupting the NA synthesis pathway.
- Reserpine blocks the vesicular monoamine transporter (VMAT), preventing dopamine from being transported from the cytoplasm into the vesicle.
- Bretylium and guanethidine inhibit the release of NA via exocytosis into the synapse.
- Salbutamol acts as an agonist at specific beta-2 receptors, simulating their activity.
- Propranolol acts as an antagonist at specific beta receptors, blocking their activity.
- COMT-inhibitors (e.g. entacapone) and MAO inhibitors (e.g. selegeline) inhibit the breakdown of NA.
- Tricyclic antidepressants and cocaine inhibit the re-uptake of NA back into the presynaptic neuron.
Neurotransmission
- Neurotransmission involves the synthesis, storage, release, and termination of action of neurotransmitters
- Most neurotransmitters are synthesized in nerve terminals, stored in membrane-bound vesicles, and released into the synapse in response to nerve stimulation
- Neurotransmitter action is terminated either by metabolism or neuronal reuptake from the synapse
- Drugs act on specific steps in neurotransmission
Cholinergic Transmission
- Choline is transported into the nerve terminal by the choline transporter (CHT)
- Acetylcholine (ACh) is synthesized from acetyl-CoA and choline by the enzyme choline acetyltransferase (ChAT)
- ACh is transported into vesicles by a vesicle-associated transporter (VAT)
- In response to nerve stimulation, calcium influx through voltage-gated calcium channels causes exocytosis of vesicles, releasing ACh into the synapse
Adrenergic Transmission
- Tyrosine is transported into the presynaptic nerve terminal by a sodium-dependent carrier.
- Tyrosine is converted to Dopa by tyrosine hydroxylase
- Dopa is converted to Dopamine by dopa decarboxylase
- Dopamine is transported into the vesicle by the vesicular monoamine transporter (VMAT)
- Dopamine is converted to Noradrenaline (NA) by dopamine-β-hydroxylase
Catecholamine Synthesis
- Tyrosine is converted to Dopa by tyrosine hydroxylase.
- Dopa is converted to Dopamine by dopa decarboxylase.
- Dopamine is converted to Noradrenaline (NA) by dopamine-β-hydroxylase
- Noradrenaline is converted to Adrenaline by phenylethanolamine-N-methyltransferase
Catecholamine Metabolism
- Catecholamines are metabolized by catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO)
Drug Effects on Cholinergic Neurotransmission
- Botulinum toxin blocks exocytosis of synaptic vesicles, inhibiting ACh release
- Pilocarpine acts as an agonist at post-synaptic receptors
- Atropine acts as an antagonist at post-synaptic receptors
- Acetylcholinesterase inhibitors like pyridostigmine inhibit ACh breakdown by AChE
Drug Effects on Adrenergic Neurotransmission
- Breakdown of NA can be inhibited by COMT-inhibitors like entacapone, or MAO inhibitors like selegiline
- Re-uptake of NA into the presynaptic neuron can be inhibited by tricyclic antidepressants and cocaine
Non-Adrenergic, Non-Cholinergic (NANC) Neurotransmitters
- Include ATP, Substance P, nitric oxide, and dopamine
Acetylcholine Neurotransmission
- Acetylcholine (ACh) is transported from the cytoplasm into vesicles by a vesicle-associated transporter (VAT).
- When an action potential reaches the nerve terminal, it causes an influx of calcium ions (Ca²⁺) through voltage-gated Ca²⁺ channels.
- This calcium influx triggers exocytosis of the vesicles, releasing ACh into the synapse.
Adrenergic Transmission
- Tyrosine is transported into the presynaptic nerve terminal by a sodium-dependent carrier.
- Tyrosine is converted to Dopa by the enzyme tyrosine hydroxylase.
- Dopa is converted to Dopamine by the enzyme dopa decarboxylase.
- Dopamine is transported into the vesicle by the vesicular monoamine transporter (VMAT).
- Inside the vesicle, Dopamine is converted to Noradrenaline (NA) by the enzyme dopamine-β-hydroxylase.
Catecholamine Synthesis
- The rate-limiting step in catecholamine synthesis is the conversion of tyrosine to dopa, which can be inhibited by metyrosine (α-methyltyrosine).
Catecholamine Metabolism
- Catecholamines are primarily metabolized by two enzymes: catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO).
Non-Adrenergic Non-Cholinergic (NANC) Mediators
- Non-adrenergic non-cholinergic (NANC) neurotransmitters describe neurotransmitters other than noradrenaline (NA) and acetylcholine (ACh).
- Major NANC mediators in the autonomic nervous system (ANS) include:
- Nitric oxide and vasoactive intestinal peptide (VIP) in the parasympathetic NS.
- ATP and neuropeptide Y in the sympathetic NS.
- Other NANC mediators include 5-hydroxytryptamine (serotonin), GABA, and dopamine.
Drug Effects on Neurotransmission
- Drugs can interfere with neurotransmission at the following steps:
- Synthesis of neurotransmitters (NT).
- Storage of NT in vesicles.
- Release of NT into the synapse.
- Interaction of the NT with post-synaptic receptors.
- Termination of NT action.
Drug Effects on Cholinergic Neurotransmission
- Hemicholinium blocks the choline transporter from transporting choline into the nerve terminal, thus preventing ACh synthesis.
- Vesamicol blocks the vesicle-associated transporter (VAT) from transporting ACh from the cytoplasm into the vesicle.
Drug Effects on Adrenergic Neurotransmission
-
Synthesis of NT:
- Metyrosine inhibits the conversion of tyrosine to dopa.
-
Storage of NT in vesicles:
- Reserpine blocks the vesicular monoamine transporter (VMAT), preventing dopamine from entering the vesicle.
-
Release of NT into the synapse:
- Release of NA via exocytosis is inhibited by bretylium and guanethidine.
-
Interaction of the NT with post-synaptic receptors:
- Drugs can act as agonists or antagonists at specific receptor subtypes.
- Termination of NT action:
- Breakdown of NA can be inhibited by COMT-inhibitors (e.g., entacapone) or MAO inhibitors (e.g., selegeline).
- Tricyclic antidepressants and cocaine inhibit the re-uptake of NA back into the presynaptic neuron.
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Test your knowledge on autonomic neurotransmission and cholinergic transmission. This quiz covers the synthesis, storage, release, and termination of neurotransmitters, and their mechanisms within the autonomic nervous system. Explore the roles of key neurotransmitters and their drug interactions.