Understanding Cholinergic Transmission in Neurohumoral Signaling
Cholinergic transmission plays a crucial role in neurohumoral signaling, involving the release of acetylcholine at synapses and neuroeffector junctions. Dr. Rashmi Rekha Kumari explains the synthesis, storage, release, and catabolism of acetylcholine, highlighting the role of choline acetyl transferase in the final step of its synthesis. Discover the sites of cholinergic transmission and the mechanisms behind the transport of choline for neurotransmission.
- Cholinergic transmission
- Neurohumoral signaling
- Acetylcholine synthesis
- Choline acetyl transferase
- Neurotransmitter
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Cholinergic Cholinergic transmission(Part transmission(Part- -I) I) Dr. Rashmi Rekha Kumari Asstt. Prof, Deptt. Of Pharmacology & Toxicology,BVC,Patna-14
Cholinergic transmission Cholinergic transmission Neurohumoral transmission either at synapse or neuroeffector junction in which acetylcholine act as a humoral agent(neurotransmitter) for transmission of action potential across the junction Dale and his colleagues discovered its transmitter role in the1930. The different sites of cholinergic transmission are 1. Parasympathetic neuroeffector junctions(Post ganglionic parasympathetic fiber) 2.Autonomic ganglia (Preganglionic parasympathetic and Preganglionic sympathetic fiber) 3.Adrenal medulla (preganglionic parasympathetic) 4. Somatic myoneural junctions 5. Certain regions of CNS. 6. Post ganglionic sympathetic fiber to sweat gland
Synthesis, Storage, Release & Catabolism of Acetylcholine
Choline acetyl transferase catalyse the final step in synthesis of acetylcholine-The acetylation of choline with acetyl coenzyme A Choline acetyl transferase is synthesised in perikaryon and then is transported along the length of axon to its terminal Axonal terminal contain large amount of mitochondria, where acetyl CoA is synthesised, Choline is taken up from extracellular fluid into axoplasm by active transport. The final step in the synthesis occur within the cytoplasm. Following synthesis most of the Ach is sequestered in synaptic vesicle Uptake of choline is rate limiting step in biosynthesis of Acetylcholine
Transport of choline from extracellular fluid to cytoplasm is inhibited by hemicholinium Ach is packaged into synaptic vesicle at high concentration by carrier mediated transport( blocked by vesamicol) Ach release occurs by Ca2+- mediated exocytosis. At neuromuscular junction, one presynaptic nerve impulse releases 100-500 vesicles. At NMJ, Ach acts on nicotinic receptors to open cation channel, producing a rapid depolarisation(end plate potential), which normally produce an action potential in muscle fiber Transmission at other fast cholinergic synapses(e.g. ganglionic) are similar
CAT: Choline acetyltransferase
Acetylcholine esterase( Acetylcholine esterase(AchE AchE) ) After serving the transmitter function, ACh within the junctional space is rapidly inactivated by hydrolysis by a specific enzyme, acetylcholine esterase (AChE). AChE is present in cholinergic nerves, autonomic ganglia and neuromuscular & neuroeffector junctions. AchE is bound to the basement membrane that lies between the pre and post synaptic membrane.
At fast cholinergic synapse (neuromuscular and ganglionic synapse) but not at slow ones (smooth muscle, gland, heart etc) the released Ach is hydrolysed by AChE very rapidly( within 1ms), so that it act very briefly. A pseudocholinesterase) is present in serum and other body tissues. It is primarily synthesized in the liver and its likely vestigial physiological function is the hydrolysis of ingested esters from plant sources. somewhat similar enzyme, butyrylcholinesterase (a
Differences between two types of cholinesterases Acetylcholinesterase (True Cholinesterase) All cholinergic sites, RBCs, gray matter. Butyrylcholinesterase (Pseudo-cholinesterase) Plasma, liver, intestine, white matter (i) Distribution (ii) Hydrolysis ACh Methacholine Benzoylcholine Butyrylcholine Very fast (in microseconds) Slower than ACh Not hydrolyzed Not hydrolyzed Slow Not hydrolyzed Hydrolyzed Hydrolyzed (iii) Inhibition More sensitive to Physostigmine More sensitive to organophosphates Termination of ACh action (iv) Function Hydrolysis of ingested esters.
