This document summarizes neurotransmitters and neuromodulators. It discusses how nerve endings called transducers convert electrical to chemical energy by synthesizing and storing neurotransmitters in vesicles. Upon stimulation, vesicles release neurotransmitters into the synaptic cleft to act on receptors and be removed. Neuromodulators modify neurotransmitter effects. Transmitters are divided into small molecules like acetylcholine, serotonin, catecholamines, and amino acids, as well as large neuropeptides. Specific locations of different transmitters are highlighted. Biosynthesis, release, and effects of various transmitters are described, including excitatory glutamate and inhibitory GABA and glycine. Finally, comparisons are made between classical transmitters and neurope

1. DR.Jawad Hussain

2. `
 Nerve endings called biological transducers that convert
electrical energy into chemical energy.
 This conversion process involves the synthesis of the
neurotransmitters, their storage in synaptic vesicles, and
their release by the nerve impulses into the synaptic cleft.
 The secreted transmitters then act on appropriate receptors
on the membrane of the postsynaptic cell and are rapidly
removed from the synaptic cleft by diffusion, metabolism,
and, in many instances, reuptake into the presynaptic
neuron.

3. `
 Some chemicals released by neurons have little or no
direct effects on their own but can modify the effects
of neurotransmitters.
 These chemicals are called neuromodulators

4.  Neurotransmitters and neuromodulators can be
divided into two major categories:
1.small-molecule transmitters and
2. large-molecule transmitters.
 Small-molecule transmitters include monoamines
(eg, acetylcholine, serotonin, histamine),
catecholamines
(dopamine, norepinephrine, and epinephrine),
and amino acids
(eg, glutamate, GABA, glycine).

5. `
 Large-molecule transmitters include a large number of
peptides called neuropeptides including substance P,
enkephalin, vasopressin.

6. There are also other substances thought to be released into the synaptic cleft to act as either
a transmitter or modulator of synaptic transmission. These include purine derivatives like
adenosine and adenosine triphosphate (ATP) and a gaseous molecule, nitric oxide (NO).

7. Four diffusely connected systems of central neurons using modulatory
transmitters. A) Norepinephrine-containing neurons. B) Serotonin-containing neurons.
C) Dopamine-containing neurons. D) Acetylcholine-containing neurons

8. NEUROTRANSMITTERS

9. MONOAMINES
 ACETYLCHOLINE
 Acetylcholine( acetyl ester of choline)----that release
acetylcholine (cholinergic neurons).
 Synthesis of acetylcholine involves the reaction of
choline with acetate.

10. LOCATION
 Acetylcholine is the transmitter at the
1. Neuromuscular junction
2. Autonomic ganglia
3. Postganglionic parasympathetic
nerve-target organ junctions and some postganglionic
sympathetic nerve-target junctions.
4. In the brain, including the basal
forebrain complex and pontomesencephalic cholinergic
complex .

11. Cholinesterases
Acetylcholine must be rapidly removed from the synapse if repolarization is to occur. The
removal occurs by way of hydrolysis of acetylcholine to choline and acetate, a reaction
catalyzed by the enzyme acetylcholinesterase.

12. Serotonin
 Serotonin is formed in the body by hydroxylation and
decarboxylation of the essential amino acid
tryptophan.
 After release from serotonergic neurons, much of the
released serotonin is recaptured inactivated by
monoamine oxidase (MAO) to form 5-
hydroxyindoleacetic acid (5-HIAA).
 This substance is the principal urinary metabolite of
serotonin.

13. LOCATION
 Serotonin (5-hydroxytryptamine; 5-HT) is present
 1. Blood platelets and in gastrointestinal tract,
where it is found in the enterochromaffin cells and the
myenteric plexus.
 2. Brain stem in the midline raphé nuclei which
project to portions of the hypothalamus, the limbic
system, the neocortex, the cerebellum, and the spinal
cord.

16. CATECHOLAMINES
Norepinephrine & Epinephrine:
 The chemical transmitter present at most sympathetic
postganglionic endings is norepinephrine.
 Norepinephrine and epinephrine, are secreted by
the adrenal medulla.
 There are also norepinephrine-secreting and
epinephrine-secreting neurons in the brain.

17. Biosynthesis & Release of
Catecholamines
 The principal catecholamines found in the
body—norepinephrine, epinephrine, and
dopamine—are formed by hydroxylation and
decarboxylation of the amino acid tyrosine.

18. Excitatory & Inhibitory
Neuorotransmitters
GLUTAMATE
 The amino acid glutamate , excitatory
transmitter in the brain and spinal cord.
 Glutamate is formed by reductive amination of
the Krebs cycle intermediate -ketoglutarate in
the cytoplasm.

19. GABA
 GABA ---- inhibitory mediator in the brain
 responsible for presynaptic inhibition.
 formed by decarboxylation of glutamate.
 The enzyme that catalyzes this reaction is glutamate
decarboxylase (GAD), which is present in nerve endings
in many parts of the brain.

20. GLYCINE
 Glycine has both excitatory and inhibitory effects in
the CNS.
 Glycine is responsible direct inhibition, primarily in
the brain stem and spinal cord.

21. `
Three kinds of neurons are responsible for direct
inhibition in the spinal cord:
 1. Neurons that secrete glycine,
 2.Neurons that secrete GABA, and
 3.Neurons that secrete both.

22. Large-Molecule Transmitters:
Neuropeptides

23. NEUROPEPTIDE
 Any of the molecules composed of short chains of
amino acids (endorphins, enkephalins, vasopressin,
etc.)
 Chains of 2 to 40 amino acids
 Stored in axon terminal as larger secretory granules (called
dense-core vesicles)
 Act at lower concentrations
 Longer lasting effects
 Some function as hormones
 Modify actions of neurotransmitters
 To date there are around fifty peptides, which are known to
act as neuronal messengers.
 Substance P, gastrin, cholecystokinin (CCK) neuropeptide Y,
enkephalin and endorphoin.

24. CHEMICAL STRUCTURE

25. COMPARISON OF CLASSICAL NEUROTRANSMITTER AND
NEUROPEPTIDE
IN LENGTH
SITE OF SYNHESIS CYTOSOL OF SYNAPTIC
KNOB
ENDOPLASMIC RETICULUM
AND GOLGI COMPLEX IN
CELL BODY TRAVEL TO
SYNAPTIC KNOB BY AXONAL
TRANSPOR
SITE OF STOTRAGE IN SMALL SYNAPTIC VESSELS
IN AXONLA TERMINALS
IN LARGE DENSE-CORE
VESICLES IN AXON TERMINAL
SPEED & DURATION OF
ACTION
RAPID, BRIEF RESPONSE SLOW; PROLONGED
RESPONSE
SITE OF ACTION SUBSYNAPTIC MEMBRANE OF
POSTSYNAPTIC CELL
NONSYNAPTIC SITES ON
EITHER PRESYNAPTIC OR
POSTSYNAPTIC CELL AT
MUCH LOWER
CONCENTERATION THAN
CLASSICAL
NEUROTRANSMITTER
EFFECT USUALLY ALTER POTENTIAL
OF POSTSYNAPTIC CELL BY
OPENING SPECIFIC ION
CHANNELS
USUALLY ENHANCE OR
SUPPRESS SYNAPTIC
EFFECTIVENESS BY LONG
TERM CHANGES IN
NEUROTRANSMITER
SYNTHESIS OR
POSTSYNAPTIC RECEPTOR
SIES

26. How Do Newly Synthesis Proteins (NTs) travel to the
Axon Terminal So Quickly?
Micotubules and motor proteins are needed for transport of
vesicles quickly to the axon terminal or synaptic knob.
Newly synthesized membrane and secretory proteins
destined for the axon travel by fast anterograd transport

27. What is Retrograde transport?
 This is transport in the opposite direction.
 Used mainly to transport “empty” vesicles to soma for
reloading purposes.
 Again, motor proteins and microtubules work are at
instrumental here.