acetyicholine
Introduction
The Autonomic Nervous System is further divided as parasympatketic (cholinergic) systeim and sympathetic (adrenergic) system.
Drugs that elicit either direct or indirect effects, similar to those profuced by acetyicholine (ACh) are known as in nerve tissues, cholinergic synapses, and in the intestinal wall. ACh stimulates the cholinergic receptors by binding to the enzymes released by nerve impulses.
The Autonomic Nervous System is further divided as parasympatketic (cholinergic) systeim and sympathetic (adrenergic) system.
Drugs that elicit either direct or indirect effects, similar to those profuced by acetyicholine (ACh) are known as in nerve tissues, cholinergic synapses, and in the intestinal wall. ACh stimulates the cholinergic receptors by binding to the enzymes released by nerve impulses.
cholinergic agents. The synthesis of ACh takes place ACh produces nicotinic and muscarinic effects. Effects thai are similar to those produced by nicotine on ganglia and the motor end plate are known as nicotinic effects.
Cholinergic transmission
occurs via ACh which acts as chemical transmitier at the following sites
occurs via ACh which acts as chemical transmitier at the following sites
1)All fibres arising from CNS (preganglionic sympathetic and parasympathetic, nerve to adrenal medulla and somatic nerves).
2) All postganglionic parasympathetic and some postganglionic sympathetic (to sweat glands and some vessels)
3) Some tracts in CNS, e.g., basal ganglia
2) All postganglionic parasympathetic and some postganglionic sympathetic (to sweat glands and some vessels)
3) Some tracts in CNS, e.g., basal ganglia
The synthesis of ACh takes place in the cytoplasm. It is synthesised by the action of enzyme choline acetyl transferase on choline and active acetate. Choline is trausported by a membrane carried mechanism from the extracellular fluid into the neuronal terminal. ACh is stored inside vesicles near the synaptic portion of the cell membrane, along with ATP and proteoglycans.
Biosynthesis of Acetylcholine
Acetylcholine constitute of two major constituents, Acetyl coenzyme A (acety! CoA. CH, CO-PS-CoA) and choline (trimethyl hydroxy ethyl aminonium hydroxide) make up ACh.
Acetyl-cnenzyme A (acetyl-CoA) is synthesised in mitochondria of cholinergic nerves Pyruvic acid or pyruvate molecules are used in the synthesis of acetyl-CotA canrter sysiem transports choline from extracellular fluid to the cytoplasm of cholinergic neurons.
This mer system is dependent on encrgy for ita action. The acetate of acetyl-CoA combites with choline in the presence of enzyme choline acetyltransferase, within the azoplesm of cholincrgic nerves and resulting in the formation of ACh.
Just like NE,an active transport system transports the newly formed ACh to the presynaptic vesicles for storage and release.
Uptake of choline by presynaptic neurons is the rate limiting step in synthesis of ACh. Transport of choline is blocked by hemicholinium and the release of presynaptic neuronal ends is blocked by botulinum toxin.
Storage and Release of Acetylcholine
Once the ACh molecules are synthesised and are stored in the synaptic vesicles. ACh is released by the bursting of these vesicles whenever needed.
The arrival of an action potential at the nerve ending opens the voltage sensitive calcium channels located on the presynaptic membrane. Thus, the concentration of calcium within the cells increases, thereby resulting in the release of contents of the vesicles (hence ACh) into the synaptic cleft. A biological response is evoked by the released ACh which binds either to the postsynaptic receptors on the postsynaptic neuron or to the effector organ.
The following are the sites for the release of ACh:
i) All preganglionic nerve endings in both parasympathetic and sympathetic nervous bat system.
2) Postganglionic nerve terminals of parasympathetic nerves.
3) Preganglionic nerve terminal of parasympathetic nerves.
4) At neuromuscular juncuons in the somatic nervous system.
5) At sympathetic nerve endings supplying few sympathetic organs. E.g.sweat glands.
6 In CNS (in Alzheimer di ease, there is a significant loss of cholinergic neurons in CNS and anticholinesterases are used to treat the condition).
The arrival of an action potential at the nerve ending opens the voltage sensitive calcium channels located on the presynaptic membrane. Thus, the concentration of calcium within the cells increases, thereby resulting in the release of contents of the vesicles (hence ACh) into the synaptic cleft. A biological response is evoked by the released ACh which binds either to the postsynaptic receptors on the postsynaptic neuron or to the effector organ.
The following are the sites for the release of ACh:
i) All preganglionic nerve endings in both parasympathetic and sympathetic nervous bat system.
2) Postganglionic nerve terminals of parasympathetic nerves.
3) Preganglionic nerve terminal of parasympathetic nerves.
4) At neuromuscular juncuons in the somatic nervous system.
5) At sympathetic nerve endings supplying few sympathetic organs. E.g.sweat glands.
6 In CNS (in Alzheimer di ease, there is a significant loss of cholinergic neurons in CNS and anticholinesterases are used to treat the condition).
Metabolism of Acetylcholine
Metabolism of ACh involves the following steps:
Metabolism of ACh involves the following steps:
1.Destruction of ACh occurs very ratidly at the nemromuscular junction, bui in the smooth muscles, its destruction ors over a comparatively longer time (30ms.)
2) The enzyme Acetylcholinesterase (AChE) is responsible for the destruction of AC by a mechanism known as hydrolysis, resulting in the formation of acetyl CoA and choline.
3) ACHE (also referred to as true choiine esterase) is found in rich amounts in the neuromuscular junction, postganglionic parasympathetic nerve terminal and ANS ganglia.
2) The enzyme Acetylcholinesterase (AChE) is responsible for the destruction of AC by a mechanism known as hydrolysis, resulting in the formation of acetyl CoA and choline.
3) ACHE (also referred to as true choiine esterase) is found in rich amounts in the neuromuscular junction, postganglionic parasympathetic nerve terminal and ANS ganglia.
4) A similar enzyme known as butyryl choline esterase (abbreviated as ChE) present in body tissues like plasma, liver, and glial cells of the brain but not in the end of neurons. Butyryl choline esterase is also known as pseudocholine esterase or serum esterase.
5) Therefore, human body houses two types of cholinesterases
i) True Cholinesterase: Hydrolysis of ACh occurs by true cholinesterases. Some ACh-related drugs such as methacholine are also hydroly ed by this enzyme However, most other esters of choline are resistant to ACh hydrolysis
2)Pseudocholine Esterase: Many esters (drugs/insecticides) are hydrolysed by pseudo cholinesterase.
6) Thus, the hydrolysis of ACh by AChE enzyme results in the formation of choline st the synaptic cleft. The choline thus released, enters the nearon again (from where the ACh was released). The re-entry of hemicholinium is inhibited by choline.
5) Therefore, human body houses two types of cholinesterases
i) True Cholinesterase: Hydrolysis of ACh occurs by true cholinesterases. Some ACh-related drugs such as methacholine are also hydroly ed by this enzyme However, most other esters of choline are resistant to ACh hydrolysis
2)Pseudocholine Esterase: Many esters (drugs/insecticides) are hydrolysed by pseudo cholinesterase.
6) Thus, the hydrolysis of ACh by AChE enzyme results in the formation of choline st the synaptic cleft. The choline thus released, enters the nearon again (from where the ACh was released). The re-entry of hemicholinium is inhibited by choline.
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