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Neurotransmitters

 Dr. M. Jawad Hassan
Objectives
1- Outline the criteria that need to be met before a
   molecule can be classified as “neurotransmitter”

2- Identify the major neurotransmitter types

3- Describe the major biochemical pathways for
   neurotransmitter synthesis and degradation

4- Identify some clinical disorders that can arise as a
   result of disruption of neurotransmitter metabolism
NEUROTRANSMITTERS
Chemical transducers which are released by
electrical impulse into the synaptic cleft from
pre-synaptic membrane from synaptic
vesicles.

They then diffuse to the post-synaptic
membrane and react and activate the
receptors present leading to initiation of new
electrical signals.
                                                  4
5
7
8
Types of responses on postsynaptic
                membrane

• Excitatory postsynaptic potential (EPSPs)
It is caused by depolarization.

• Inhibitory Postsynaptic potential (IPSPs)
It is caused by hyper-polarization.
NMDA =N methyl-D-aspartate receptors, when glutamate & glycine bind to
receptor ion channels open, Mg block channels
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.
Glycine
• It is simplest of all aminoacids, consisting of
  amino group and a carboxyl group attached to
  a carbon atom
                       H+



              H3 N+     C       H+



                       Coo-
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.
Histamine
• Three known types of histamine receptors in found
  e.g. H1, H2, H3.

• H3 receptors are pre-synaptic. Its function in brain is
  not very certain. Its main function is that it is
  excitatory.
Nitric Oxide (NO)
• NO is produced by arginine

• Relax vascular and intestinal s. muscles

• Role in mitochondrial energy production

• Role in memory formation

• Increased in Parkinson's and Alzheimer's
  disease
Postsynaptic                            Site of       Postsynaptic
Neurotransmitter                     Derived from                                              Fate                Functions
                       effect                              synthesis        receptor
1.Acetyl choline    Excitatory      Acetyl co-A +       Cholinergic       •Nicotinic     Broken by acetyl     Cognitive functions
(Ach)                               Choline             nerve endings     •Muscarinic    cholinesterase       e.g. memory
                                                        Cholinergic                                           Peripheral action e.g.
                                                        pathways of                                           cardiovascular
                                                        brainstem                                             system
2. Catecholamines   Excitatory in   Tyrosine            Adrenal           Excites both   •Catabolized to      For details refer
i. Epinephrine      some but        produced in liver   medulla and       alpha α &      inactive product     ANS. e.g. fight or
(adrenaline)        inhibitory in   from                some CNS          beta β         through COMT &       flight, on heart,
                    other           phenylalanine       cells             receptors      MAO in liver         BP, gastrointestinal
                                                                                         •Reuptake into       activity etc.
ii.Norepinephrine   Excitatory      Tyrosine, found     Begins inside     α1 α2
                                                                                         adrenergic nerve     Norepinehrine
                                    in pons.            axoplasm of       β1 β2          endings              controls attention &
                                    Reticular           adrenergic
                                                                                         •Diffusion away      arousal.
                                    formation, locus    nerve ending is
                                                                                         from nerve endings
                                    coerules,           completed
                                                                                         to body fluid
                                    thalamus, mid-      inside the
                                    brain               secretary
                                                        vesicles
iii. Dopamine       Excitatory      Tyrosine            CNS,              D1 to D5       Same as above        Decreased dopamine
                                                        concentrated in   receptor                            in parkinson’s
                                                        basal ganglia                                         disease.
                                                        and dopamine                                          Increased dopamine
                                                        pathways e.g.                                         concentration causes
                                                        nigrostriatal,                                        schizophrenia
                                                        mesocorticolim
                                                        bic and tubero-
                                                        hypophyseal
                                                        pathway
Postsynaptic                           Site of            Postsynaptic
Neurotransmitter                   Derived from                                                       Fate                  Functions
                      effect                             synthesis             receptor
  3. serotonin     Excitatory     Tryptophan          CNS, Gut           5-HT1 to    5-HT     Inactivated by MAO       Mood control, sleep,
      (5HT)                                           (chromaffin                             to form 5-               pain feeling,
                                                                         7
                                                      cells) Platelets   5-HT 2 A             hydroxyindoleacetic      temperature, BP, &
                                                      & retina                                acid(5-HIAA) in          hormonal activity
                                                                         receptor mediate
                                                                                              pineal body it is
                                                                         platelet
                                                                                              converted to
                                                                         aggregation &
                                                                                              melatonin
                                                                         smooth muscle
                                                                         contraction
4. Histamine       Excitatory     Histidine           Hypothalamus       Three types H1,      Enzyme diamine           Arousal, pain
                                                                         H2 ,H3 receptors     oxidase                  threshold, blood
                                                                         found in             (histaminase) cause      pressure, blood flow
                                                                         peripheral tissues   breakdown                control, gut
                                                                         & the brain                                   secretion, allergic
                                                                                                                       reaction (involved in
                                                                                                                       sensation of itch)
5. Glutamate       Excitatory     By reductive        Brain & spinal     Ionotropic and       It is cleared from the   Long term
                   75% of         amination of        cord e.g.          metabotropic         brain ECF by Na +        potentiation involved
                   excitatory     Kreb’s cycle        hippocampus        receptors.           dependent uptake         in memory and
                   transmission   intermediate                           Three types of       system in neurons        learning by causing
                   in the brain   α –ketoglutarate.                      ionotropic           and neuroglia.           Ca++ influx.
                                                                         receptors e.g.
                                                                         NMDA, AMPA
                                                                         and kainate
                                                                         receptors.
Postsynaptic                        Site of      Postsynaptic
Neurotransmitter                   Derived from                                                  Fate                   Functions
                      effect                          synthesis       receptor

                                                                                        Aspartate & Glycine form an excitatory /
6. Aspartate       Excitatory     Acidic amines      Spinal cord   Spinal cord
                                                                                        inhibitory pair in the ventral spinal cord

                                                                   GABA – A
                                                                   increases the Cl -                             GABA – A causes
                                                                   conductance,                                   hyperpolarization
                                  Decarboxylation                  GABA – B is                                    (inhibition)
                                  of glutamate by                  metabotropic                                   Anxiolytic drugs like
                                                                                        Metabolized by
7. Gama amino      Major          glutamate                        works with G –                                 benzodiazepine cause
                                                                                        transamination to
butyric            inhibitory     decarboxylase      CNS           protein GABA                                   increase in Cl- entry
                                                                                        succinate in the citric
acid(GABA)         mediator       (GAD) by                         transaminase                                   into the cell & cause
                                                                                        acid cycle.
                                  GABAergic                        catalyzes.                                     soothing effects.
                                  neuron.                          GABA – C                                       GABA – B cause
                                                                   found                                          increase conductance
                                                                   exclusively in                                 of K+ into the cell.
                                                                   the retina.


                                                                                        Deactivated in the
                                  Is simple amino                  Glycine receptor                               Glycine is inhibitory
                                                                                        synapse by simple
                                  acid having                      makes                                          transmitted found in
                                                                                        process of
                                  amino group and                  postsynaptic                                   the ventral spinal
8. Glycine         Inhibitory                        Spinal cord                        reabsorbtion by active
                                  a carboxyl group                 membrane more                                  cord. It is inhibitory
                                                                                        transport back into
                                  attached to a                    permeable to Cl-                               transmitter to
                                                                                        the presynaptic
                                  carbon atom                      ion.                                           Renshaw cells.
                                                                                        membrane
QUESTIONS?
THANK YOU

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Neurotransmitters dr. jawad class of 2015

  • 2. Objectives 1- Outline the criteria that need to be met before a molecule can be classified as “neurotransmitter” 2- Identify the major neurotransmitter types 3- Describe the major biochemical pathways for neurotransmitter synthesis and degradation 4- Identify some clinical disorders that can arise as a result of disruption of neurotransmitter metabolism
  • 3.
  • 4. NEUROTRANSMITTERS Chemical transducers which are released by electrical impulse into the synaptic cleft from pre-synaptic membrane from synaptic vesicles. They then diffuse to the post-synaptic membrane and react and activate the receptors present leading to initiation of new electrical signals. 4
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  • 9. Types of responses on postsynaptic membrane • Excitatory postsynaptic potential (EPSPs) It is caused by depolarization. • Inhibitory Postsynaptic potential (IPSPs) It is caused by hyper-polarization.
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  • 20. NMDA =N methyl-D-aspartate receptors, when glutamate & glycine bind to receptor ion channels open, Mg block channels
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  • 22. 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.
  • 23. Glycine • It is simplest of all aminoacids, consisting of amino group and a carboxyl group attached to a carbon atom H+ H3 N+ C H+ Coo-
  • 24.
  • 25. 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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  • 31. Histamine • Three known types of histamine receptors in found e.g. H1, H2, H3. • H3 receptors are pre-synaptic. Its function in brain is not very certain. Its main function is that it is excitatory.
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  • 36. Nitric Oxide (NO) • NO is produced by arginine • Relax vascular and intestinal s. muscles • Role in mitochondrial energy production • Role in memory formation • Increased in Parkinson's and Alzheimer's disease
  • 37. Postsynaptic Site of Postsynaptic Neurotransmitter Derived from Fate Functions effect synthesis receptor 1.Acetyl choline Excitatory Acetyl co-A + Cholinergic •Nicotinic Broken by acetyl Cognitive functions (Ach) Choline nerve endings •Muscarinic cholinesterase e.g. memory Cholinergic Peripheral action e.g. pathways of cardiovascular brainstem system 2. Catecholamines Excitatory in Tyrosine Adrenal Excites both •Catabolized to For details refer i. Epinephrine some but produced in liver medulla and alpha α & inactive product ANS. e.g. fight or (adrenaline) inhibitory in from some CNS beta β through COMT & flight, on heart, other phenylalanine cells receptors MAO in liver BP, gastrointestinal •Reuptake into activity etc. ii.Norepinephrine Excitatory Tyrosine, found Begins inside α1 α2 adrenergic nerve Norepinehrine in pons. axoplasm of β1 β2 endings controls attention & Reticular adrenergic •Diffusion away arousal. formation, locus nerve ending is from nerve endings coerules, completed to body fluid thalamus, mid- inside the brain secretary vesicles iii. Dopamine Excitatory Tyrosine CNS, D1 to D5 Same as above Decreased dopamine concentrated in receptor in parkinson’s basal ganglia disease. and dopamine Increased dopamine pathways e.g. concentration causes nigrostriatal, schizophrenia mesocorticolim bic and tubero- hypophyseal pathway
  • 38. Postsynaptic Site of Postsynaptic Neurotransmitter Derived from Fate Functions effect synthesis receptor 3. serotonin Excitatory Tryptophan CNS, Gut 5-HT1 to 5-HT Inactivated by MAO Mood control, sleep, (5HT) (chromaffin to form 5- pain feeling, 7 cells) Platelets 5-HT 2 A hydroxyindoleacetic temperature, BP, & & retina acid(5-HIAA) in hormonal activity receptor mediate pineal body it is platelet converted to aggregation & melatonin smooth muscle contraction 4. Histamine Excitatory Histidine Hypothalamus Three types H1, Enzyme diamine Arousal, pain H2 ,H3 receptors oxidase threshold, blood found in (histaminase) cause pressure, blood flow peripheral tissues breakdown control, gut & the brain secretion, allergic reaction (involved in sensation of itch) 5. Glutamate Excitatory By reductive Brain & spinal Ionotropic and It is cleared from the Long term 75% of amination of cord e.g. metabotropic brain ECF by Na + potentiation involved excitatory Kreb’s cycle hippocampus receptors. dependent uptake in memory and transmission intermediate Three types of system in neurons learning by causing in the brain α –ketoglutarate. ionotropic and neuroglia. Ca++ influx. receptors e.g. NMDA, AMPA and kainate receptors.
  • 39. Postsynaptic Site of Postsynaptic Neurotransmitter Derived from Fate Functions effect synthesis receptor Aspartate & Glycine form an excitatory / 6. Aspartate Excitatory Acidic amines Spinal cord Spinal cord inhibitory pair in the ventral spinal cord GABA – A increases the Cl - GABA – A causes conductance, hyperpolarization Decarboxylation GABA – B is (inhibition) of glutamate by metabotropic Anxiolytic drugs like Metabolized by 7. Gama amino Major glutamate works with G – benzodiazepine cause transamination to butyric inhibitory decarboxylase CNS protein GABA increase in Cl- entry succinate in the citric acid(GABA) mediator (GAD) by transaminase into the cell & cause acid cycle. GABAergic catalyzes. soothing effects. neuron. GABA – C GABA – B cause found increase conductance exclusively in of K+ into the cell. the retina. Deactivated in the Is simple amino Glycine receptor Glycine is inhibitory synapse by simple acid having makes transmitted found in process of amino group and postsynaptic the ventral spinal 8. Glycine Inhibitory Spinal cord reabsorbtion by active a carboxyl group membrane more cord. It is inhibitory transport back into attached to a permeable to Cl- transmitter to the presynaptic carbon atom ion. Renshaw cells. membrane
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