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
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.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20. NMDA =N methyl-D-aspartate receptors, when glutamate & glycine bind to
receptor ion channels open, Mg block channels
21.
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.
26.
27.
28.
29.
30.
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.
32.
33.
34.
35.
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