NEUROTRANSMITTERS

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NEUROTRANSMITTERS

• Dr Fawzia ALRoug, MBBS, Master, Ph.D
• Assistant Professor, Department of Physiology,
  College of Medicine, King Khalid University
  Hospital, Riyadh, Saudi Arabia

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NEUROTRANSMITTERS

• DEFINITION Are chemical transducers which are
  released by electrical impulse into the synaptic
  cleft from presynaptic membrane from synaptic
  vesicles. It then diffuse to the postsynaptic
  membrane and react and activate the receptors
  present leading to initiation of new electrical
  signals.

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Discovery of neurotransmitters

• Loewi, 1921
• frog hearts in saline solution
• Stimulation of vagus nerve results in lower heart
  rate
• gave long vagal nerve stimulation
• Heart 2
• Exposed to saline solution from heart 1
• Slowed heart rate
• Conclusion Neurotransmission is chemical
• nerve releases chemical that can influence other
  cells

Fig 8.1, Zigmond Fundamental Neuroscience
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Fate of neurotransmitters

• Are as ,
• It is consumed ( broken down or used up) at
  postsynaptic membrane leading to action potential
  generation.
• Degraded by enzymes present in synaptic cleft.
• Reuptake mechanism( reutilization) this is the
  most common fate.

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Types of responses on postsynaptic membrane

• Excitatory postsynaptic potential (EPSPs)
• It is caused by depolarization.
• Inhibitory Postsynaptic potential (IPSPs)
• It is caused by hyperpolarization.

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Fast Slow Postsynaptic potentials

• Fast EPSPs IPSPs work through ligand gated ion
  channels.eg. Nicotinic receptors(at the level of
  neuromuscular junction)
• Slow EPSPs IPSPs are produced by multi step
  process involving G protein eg. Muscarinic
  receptors ( at the level of autonomic gangila)

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Acetyl Choline Receptors
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MAOmonoamine oxidase ,COMTcatechole-o-methyle-tr
ansferase
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Formation of serotonin 5-HT Hydroxy
tryptamine HIAAhydroxyindoleacetic acid
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Histamine

• Histamine forming cells are in posterior
  hypothalamus also found in gastric mucosa and in
  mast cells.
• Formed by decarboxylation of amino acid
  histidine with the help of enzyme histaminase.
• Three known types of histamine receptors in found
  e.g. H1, H2, H3.
• H3 receptors are presynaptic. Its function in
  brain is not very certain. Its main function is
  that it is excitatory.

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Glycine

• It is simplest of all aminoacids, consisting of
  amino group and a carboxyl group attached to a
  carbon atom

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Glycine..

• Its an inhibitory neurotransmitter.
• It binds to a receptor which makes the post
  synaptic membrane more permeable to Cl- Ion and
  cause hyperpolarization (inhibition).
• The glycine receptor is primarily found in the
  ventral part of the spinal cord.
• Strychnine is glycine antagonist.

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Glutamic acid

• It is the most commonly found neurotransmitter in
  the brain.
• It is always excitatory.
• Glutamate is formed during Krebs cycle for a
  ketoglutarate.
• Glutamate is carried into astrocytes where it is
  converted to glutamine and passed on to
  glutaminergic neurones.
• Glutamate is neurotoxic while glutamine is not.
• There are two types of receptors e.g.
  metabotropic and iontropic receptors.

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NMDA N methyl-D-aspartate receptors, when
glutamate glycine bind to receptor ion channels
open, Mg block channels
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Gamma Aminobutyric acid(GABA)

• It is one of the inhibitory neurotransmitter of
  CNS and is also found in retina.
• It is formed by decarboxylation of glutamate.
• The enzyme that catalyzes this reaction is
  glutamate decarboxylase(GAD)
• There are three types of GABA receptors e.g.
  GABAA B C.
• GABA A B receptors are widely distributed in
  CNS.
• GABAC are found in retina only.
• GABA B are metabotropic (G-protein) in function.

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RECEPTORS DYSFUNCTION

• Presynaptic effect
• i) Botulinum toxin Its an exotoxin that binds to
  the presynaptic membrane and prevents the release
  of Ach resulting in weakness and reduction of
  tone. It is used to control dystonia in which
  body shows overactive muscular activity.

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• ii) Lumbert Eaton syndrome
• Antibodies directed against Ca channels located
  in presynaptic terminals and interfere with
  transmitter release causing weakness.
• iii)Neuromyotonia
• Patient complains of muscle spasm and stiffness
  resulting in continuous motor activity in the
  muscle. It is cased by antibody directed against
  the presynaptic voltage gated K channel so that
  the nerve terminal is always in a state of
  depolarization

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• 2. Effects at Postsynaptic level
• Curare binds to the acetylcholine receptor (AchR)
  and prevents Ach from acting on it and so that it
  induces paralysis.
• Myasthenia gravis is caused by an antibody
  against the Ach receptors and Ach receptors are
  reduced hence the Ach released has few Ach
  receptor available to work and patients complain
  of weakness that increases with exercise.

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Synaptic strength

• Can be facilitated like long term potentiation.
• Can be depressed ( inhibited) by long-term
  depression.

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Classification of Neurotransmitters

• Amines
• Acetyl choline (Ach)
• Monoamines
• Catecholamines
• Epinephrine
• Nor epinephrine
• Dopamine (Substantia nigra, sympathetic ganglia)

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• Serotonin ( hypothalamus, cerebellum, spinal
  cord, retina)
• Histamine ( Hypothalamus)
• Amino acids
• Excitatory eg. Glutamate ( cortex, brainstem)
• - Aspartate (visual cortex)
• Inhibitory eg. Gamma amino butaric acid GABA
  cerebrum, cerebellum presynaptic inhibitory
  neurone in retina
• - Glycine spinal cord.

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• Purine derivatives
• eg. Adinosine ATP.
• Polypeptides ( a very long list of names)
• eg. Enkephaline, hormones ( VIP etc)
• ( refer to the list in Ganong 21st edition pg.97)
  
• Nonsynaptic transmitters
• eg. Gases, nitric oxide cabon mono oxide.

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