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  1. 1. NEUROTRANSMITTERS M.Prasad Naidu MSc Medical Biochemistry, Ph.D,.
  2. 2. Neurotransmitters Definition: Neruo transmitters are endogenous chemicals which transmit signals from a neuron to target cells across a synapse.
  3. 3. Important Neuro transmitters are 1. GABA 2. Serotonin 3. Acetyl choline 4. Catecholamines Dopa Norepinephrine Epinephrine 5. Glycine 6. Glutamate
  4. 4. Miscellaneous: Nitric oxide Taurine Histamine Aspartate
  5. 5. Name of the neurotransmitter Excitatory Inhibitory 1. GABA ----- Inhibitory 2. Catecholamines Excitatory ----- 3. Glycine --- Inhibitory 4. Glutamate Excitatory ---- 5. Acetyl choline Excitatory ----- 6. Serotonin
  6. 6. GABA γ – amino butyric acid Synthesized from A.A L- glutamate by decarboxylation. Glutamate decarboxylase Glutamate GABA PLP CO2
  7. 7. Glutamate decarboxylase is present in nerve endings of the brain as well as in the β-cells of the pancreas.
  8. 8. GABA increase the permeability of post synaptic membranes to chloride ions. GABA act as neurotransmitter by opening of the chloride ion channels.
  9. 9. Glutamate Non essential Aminoacid Excitatory neurotransmitter, Neurons contain NMDA(N methyl D Aspartate ) receptors. NMDA receptors are stimulated by glutamate and opens calcium channel leading to stimulation of neuronal NOS (Nitric oxide synthase)and produces NO. NO activates guanyl cyclase, there by increasing cyclic GMP in neighboring neurons and causes excitation .
  10. 10. Glutamate NMDA receptors Activates NOS NO Guanylcyclase CyclicGMP Excitation of Neurons
  11. 11. In conditions like head injury , Huntington’s chorea etc., cerebral damage causes Excess glutamate is released in brain. This increased glutamate causes increased release of calcium, generation of free radicals and cell death.
  12. 12. Serotonin Serotonin is excitatory on motor pathways and inhibitory on sensory pathways Synthesized from tryptophan
  13. 13. Synthesis of Serotonin 5-Hydroxy tryptophan on decarboxylation produces serotonin A neurotransmitter 5-Hydroxy tryptophan SerotoninDecarboxylase
  14. 14. Tryptophan hydroxylase Decarboxylase Mono amino Oxidase Acetalyse Methyal transferase Serotonin
  15. 15. Serotonin is involved in mood changes Sleep Appetite and Temperature regulation Increases intestinal motility Decreased levels is seen in depressive psychosis.
  16. 16. Glycine Inhibitory neuro transmitter in the spinal cord. It blocks impulses traveling down in cord in motor neurons to stimulate skeletal muscle It increases chloride ions and produces hyper polarisation at post synaptic neurons Glycine potentiates the action of GABA
  17. 17. Acetyl choline First chemical neurotransmitter identified was acetylcholine Neurotransmitter between axons and striated muscle at the nueromuscular junction. Acetylcholine is synthesized in neuronal cytoplasm from choline and acetyl CoA through the action of choline acetyl trasferase.
  18. 18. Synthesis and storage Acetyl CoA is derived from pyruvate metabolism Choline molecues may be taken up from the blood or from the synaptic cleft where they have been produced by acetyl choline hydrolysis or they may be formed from the degradation of phosphatidyl choline Acetyl choline is then incorporated into synaptic vesicles and stored therein.
  19. 19. Release and action: Release of acetylcholine in response to a action potential is Ca2+ dependent. The released acetyl choline diffuse rapidly across the synaptic cleft to its receptors on the postsynaptic membrane (muscle membrane) Causing opening of the Na+ channels in the receptors that permit a flux of actions across the membranes.
  20. 20. The consequent entry of Na+ results in depolarizing the muscle membrane and action potential generated is transmitted along the fibre, resulting in contraction of the muscle.
  21. 21. Reuptake and degradation: Once released acetylcholine must be removed rapidly in order to allow repolarization to take place. When the channel closes the acetyl choline dissociates and is hydrolyzed by acetyl cholinesterase.
  22. 22. This enzyme is present in high amounts in the synaptic space. Acetyl choline may also be hydrolysed by non specific esterases called pseudo choline esterase which occurs in many tissues and in plasma. The choline released by the hydrolysis in the synaptic cleft is recycled into the nerve terminal by an active transport mechanism. Here it is used for resynthesis of acetyl choline.
  23. 23. Nitric Oxide Nitric oxide is simple gas with free radical properties but identified as a neurotransmitter. At low concentration nitric oxide carries nerve impulses from one neuron to another. Nitric oxide synthesized in synapses and used immediately.
  24. 24. Nitric oxide half life is few seconds. Synthesis of Nitric Oxide
  25. 25. DISORDERS 1. Defect in release of acetyl choline. Ex: Eaton Lambert Myasthenic Syndrome 2. Neuromuscular Disorder. Ex: Myasthenia Gravis (AChR antibodies) 3. Excess release.(Norepinephrine ,Epinephrine) Ex: Phaeochromocytoma 4. Decreased Synthesis.(Dopamine) Ex: Parkinson’s Disease. 5. Bipolar Disorders.(serotonin)
  26. 26. Histamine It is found in hypothalamus Histamine is synthesized from histidine by decarboxylation. Histamine controls release of pituitary hormones. Plays a role in sleep awake cycles and food intake (apetite)