Acetylcholine & Glutamate PDF

Acetylcholine & Glutamate Acetylcholine: - Ach synthesised from choline and acetyl coenzyme A - Choline found in high concentrations in presynaptic terminal - Primarily comes from fat in our diet, can also be produced in small amounts by the liver - Choline acetyltransferase = enzym...

Acetylcholine & Glutamate Acetylcholine: - Ach synthesised from choline and acetyl coenzyme A - Choline found in high concentrations in presynaptic terminal - Primarily comes from fat in our diet, can also be produced in small amounts by the liver - Choline acetyltransferase = enzyme required to combine acetyl coenzyme A and choline into acetylcholine - Choline acetyltransferase = only present in the cholinergic neurones - Is used at the NMJ to elicit muscle contractions, acts as a neuromodulator in brain regulating functions e.g. memory and sleep A white paper with black text Description automatically generated **Anatomy of cholinergic pathways:**  A diagram of the brain Description automatically generated Synthesis and degradation of Ach 1. Acetylcholine is synthesised from acetyl CoA and choline. 2. The newly synthesised transmitter is pumped into vesicles through ACh transporter 3. The neurotransmitter is released from vesicle upon the arrival of an action potential 4. ACh acts for a short time on postsynaptic receptors before it is degraded by AChE. 5. Choline is recycled and pumped back into the presynaptic terminal by the choline transporter 2 types of receptors: - Ionotropic - pass ions e.g. sodium - Muscarinic -- activate G proteins, activate cascades Nicotinic and muscarinic Ach receptors: - Named after nicotine and muscarinic which are full agonists for the receptor types and provide activation - Inhibitors -- curare (competitive of nictonic), atropine (of muscarinic) - Cholinergic recpeotrs named after selective agonists which mimic effects of endogenous ligand (Ach)  Nomenclature of Ach receptors and their subunits A diagram of a neuronal cell Description automatically generated with medium confidence Myasthenia gravis -- autoimmune disease:  - Is an autoimmune disease set by antibodies that are produced and they act on the receptors, means they are getting deactivated by the antibodies - In order to have a positive treatment of the symptoms, increase Ach using cholinesterase inhibitor, provides greater activation of the residual receptors 1. Antibody testing 2. Electromyography 3. Neostigmine (edrophonium) test Inhibition of Ach release reverses aging: - Botox -- injectable form of botulinum toxin - After treatment -- muscles become paralysed and remain relaxed Muscarinic Ach receptor - 5 different receptor subunit types -- m1 to M5 - Not many specific agonists of the receptor (only a specific one for M1), all other receptor types activated by nonspecific agonist - Most known carbacol and pilocarpine -- widely used for activation A list of protein supplements Description automatically generated with medium confidence - Muscarinic receptors are not far off nicotinic receptors for the beauty uses because the muscarinic antagonists include atropine (dilate pupils used for ophthalmology) and scopolamine, derived from belladonna plant - Belladonna -- produced by deadly nightshade plant -- named because ingestion of excessive amounts are dangerous - Excess use of antimuscarinic drugs produce cognitive impairment, higher doses cause delirium + tachycardia + other dangerous autonomic symptoms Ligands affecting cholinergic transmission:  A screenshot of a medical chart Description automatically generated Glutamate: Glutamate synthesis and inactivation:  - In presynaptic terminals of glutamatergic neurons, glutamine (gln) is converted to glutamate (glut) by enzyme glutaminase (1) - Alternatively -- glutamate is synthesised by transamination of aspartate by transaminase (2) - After is it released from nerve terminals -- glutamate is taken up into glila cells (3), converted into glutamine by glutamine synthetase (4) A diagram of a glutamine Description automatically generated - Glutamine then pumped out of glia by SN1 (1), taken up by nerve terminals (2), converted back to glutamate to replenish transmitter pool (3) - Uptake of glutamate into glial (+ neural) compartments achieved by glutamate transporters GLT-1, GLAST and EAAC1 (4) Glutamatergic transmission: 2 types of receptor types - iGluR -- conduct ions e..g sodium and calcium : NMDA, AMPA, KAINATE - mGluR -- split into 3 groups, group 1, group 2, group 3  A diagram of a cell membrane Description automatically generated iGluR subunits:  Activation by NMDAR, AMPAR (Quis) and Kainate R A diagram of a variety of shapes Description automatically generated with medium confidence - Shows responses of DMDAR, AMPAR and Kainate receptors to different agonists - NMDA -- no response - Gly -- no response - NMDA + Gly -- channels open and response is produced - NMDA receptors require opening and binding of both neurotransmitter types (NMDA is used for selective activation) - Glu -- produces small response - Glu + Gly -- produces large responses - Nonselective activation - Quis -- activates AMPAR receptor - Quis + Gly -- shows Gly is not involved in AMPAR transmission - Same with Kainate Ketamine; an antagonist of NMDA receptors  - When ketamine (anaesthetic) is applied -- NMDA stops producing response Types of NMDA receptors: - Conventional NMDA receptors -- 2 GluN1 subunits, 2 GluN2 subunits - Unconventional NMDARs -- incorporate GluN3 subunits + to either GluN1 or GluN2 - NMDARs either di-heteromeric (incorporates up to 2 types of different subunits) or tri-heteromeric (3 types) Conventiomal NMDARs: Diagram of a cell membrane Description automatically generated