Acetylcholine ppt
- 1. Acetylcholine Presented by: Abhishek .S. Joshi First Year M.Pharm(Pharmacology) SSR College of Pharmacy, Silvassa
- 2. 1. Introduction Acetylcholine is a chief neurotransmitter of parasympathetic nervous system which is a part of autonomic nervous system. Neurotransmitters- • Chemical messengers • Transmit a message (impulse) from one nerve to another, finally to target cell. • Target cell can be nerve cell/ muscle cell/ gland cell Nervous system can be broadly classified into two parts: CNS(central nervous system) and PNS(peripheral nervous system)
- 3. PNS- Connects CNS to various organs Efferent(Motor) neurons- Carry impulses away from CNS Afferent (sensory) neurons- Carry impulses towards the CNS Parasympathetic- Aka as Digest or rest system Sympathetic- Aka Fight or flight system Ach
- 4. Chemically Ach is an ester of acetic acid and choline. First time Ach was found or discovered in the vagus nerve hence previously it was known as “vagustoff” It was the first neurotransmitter to be identified. Two receptors are identified on which Ach acts- Nicotinic and Mucarinic
- 6. Biosynthesis Choline (an amino acid) enters presynaptic neuron along with Na+ ion through a symporter choline transporter(CHT). Mitochondria inside the neuron synthesizes and releases acetyl coenzyme A (Acetyl coA). Acetyl CoA combines with choline in the presence of enzyme ChAT (choline acetyl transferase). ChAT makes an ester bond between Acetyl CoA and Choline thus forming Aetylcholine
- 7. Storage Synthesized Ach is stored in a vesicle. VAT (vesicle associated transporter), an antiporter transports Ach into the vesicle. As Ach goes in, the H+ ion already present in the vesicle moves outside into the neuron. Each vesicle contains about 1000 to 50,000 molecules of Ach. Vesicles are provided with certain proteins- VAMPs (Vesicle associated membrane proteins) Nerve terminal ending contains SNAPs (synaptosomal nerve associated proteins) SNAPs interact with VAMPs SNAPs + VAMPs collectively- Fusion protein Main role of both the proteins are in the release of Ach
- 9. Release Physiologic release of Ach depends on Ca++ levels. Due to action potential- Ca++ influx into the neuron- increase level of Ca++ in the neuron. Ca++ attaches to VAMPs. VAMPs helps the vesicle to take certain shapes Thus vesicles fuses with the membrane. Membrane ruptures. And Ach is released into the synapse. (Exocytosis)
- 10. Metabolism Ach released from presynaptic neuron goes to postsynaptic neuron where there are cholinoceptors. Ach interacts with the receptors, generates action, then dissociates from receptors. Dissociated Ach undergoes metabolism with the help of enzyme Cholinesterase. Two types of cholinesterase available • Acetylcholinesterase (AchE): True cholinesterase, Located at all cholinergic sites, fast in action, terminates action of Ach • Butyrylcholinesterase(BuchE): Pseudocholinesterase, located in the plasma, liver and intestine, slow in action, hydrolyses the ingested ester. Ach is broken down to Acetyl CoA and Choline Acetate and choline both have no any transmitter activity.
- 11. Reuptake After metabolism, Acetyl CoA is left outside. Choline is transported back to neuron through choline transporter. Certain toxins believed to affect cholinergic transmission: Hemicholinium: Blocks choline transporter. Vesamicol: Inhibit VAT transporter. Botulinum toxin: Inhibit release of Ach
- 12. 3. Cholinergic receptors (Cholinoceptors),their locations and functions Two classes of receptors of Ach are recognized: Muscarinic and Nicotinic Muscarinic- G protein coupled receptors Nicotinic- Ligand gated ion channels
- 13. Muscarinic receptors Stimulated by muscarine, blocked by atropine Primary locations- • Heart, blood vessels, eye, smooth muscles and glands of GI, respiratory and urinary tract, sweat glands, CNS Muscarinic receptors are classified into 5 sub types (M1- M5) First 3 are major subtypes. M4 and M5 are mainly present on the nerve endings and few regions of brain, regulating the release of neurotransmitters. Functionally- M1, M3, M5 make one class and M2 and M4 a different class.
- 14. APD- Action potential duration PLA2- Phospholipase A2
- 15. Nicotinic receptors These receptors are selectively activated by nicotine and blocked by tubocurarine or hexamethonium. They are rosette-like pentameric structures which enclose a ligand gated cation channel: their activation causes opening of the channel and rapid flow of cations resulting in depolarization and an action potential. On the basis of location and selective agonists and antagonists two subtypes NM and NN are recognized
- 16. PTMA- Phenyl trimethyl ammonium DMPP- Diphenyl Methyl piperazinium
- 17. 4. Drugs acting on cholinergic receptors i. Cholinergic agonists/ Parasympathomimetics/ Cholinomimetics- These produces their action similar to that of Ach. ii. Anticholinesterase- These also produce their action similar to that of acetylcholine but they increase availability of Ach. iii. Anticholinergics/ Parasympatholytics/ Muscarinic receptor antagonist/ Atropinic- Blocks actions of Ach. iv. Ganglion blockers- Nicotinic receptor antagonists
- 18. i. Cholinergic agonists/ Parasympathomimetics/ Cholinomimetics. Heart- Hyperpolarization of SA node thus, bradycardia (reduced heart rate) or cardiac arrest Blood vessels- Dilation Smooth muscle- contraction, increased in peristalsis, constriction of bronchial muscles. Glands- Increased secretion of glands(sweat, salivation, lacrimation). Eye- Constriction of circular muscles (miosis) CNS- IV injection of Ach does not cross BBB, hence no central effect seen.
- 19. ii Anticholinesterase Anticholinesterases (anti- ChEs) are agents which inhibit ChE. These protect ACh from hydrolysis—produce cholinergic effects. Some anti ChEs have additional direct action on nicotinic cholinoceptors. Cognitive functions have been seen to improved in case of patients suffering from Alzheimers administered with AChEs.
- 20. iii Anticholinergics/ Parasympatholytics/ Muscarinic receptor antagonist/ Atropinic
- 21. These are atropine like drugs hence also atropinic. Actions are opposite to that of cholinomimetic drugs. CNS- An overall stimulant action seen by atropine. But Hyoscine produces depressant action even at low doses. Heart- Tachycardia (increased heart rate) (blockade of M2 receptor) Eye- Mydriatic effects seen (dilation of pupil) Smooth muscles- Relaxed, bronchodilation Glands- Decreased secretion of glands Body temperature- Rise in body temperature due to inhibition of sweating. Local anaesthetic- Mild
- 22. iv Ganglion blockers- Nicotinic receptor antagonists
- 23. These were used as an antihypertensive and as anti ulcer drugs in in the 1950s but now totally replaced due to number of side effects. Mecamylamine- Either alone or in combination with nicotine patch, it has been tried for smoking cessation There is at present no clinical relevance of ganglion blockers.
- 24. References Essentials of Medical Pharmacology, K.D.Tripathi, 8 Edition Essentials of Medical Pharmacology, K.D.Tripathi, 7 Edition Acetylcholinesterase Inhibitors: Pharmacology and Toxicology, Mirjana B., Aleksandra M. Bondi and Vesna M. Vasi Cholinergic Medications, Ramya S. Pakala; Kristen N. Brown; Charles V. Preuss.