دانشگاه آزاد اسلامی واحد غرب درس سروتونین

1. Serotonin
Dr
Alimadadi
MD,PHD Nutrition,
Psychiatrist
IUMS

3. • In the mid-1950s, the discovery that the pronounced
behavioral effects of reserpine are accompanied by a
profound decrease in brain 5-HT led to the proposal
that serotonin may function as a neurotransmitter in
the mammalian CNS.
• 5-hydroxytryptamine (5-HT)
• The highest concentrations were found in GI mucosa,
followed by platelets and the CNS
• Cell bodies are found in raphe nucleus, pons, and
medulla (part of the reticular formation)
• Projections are mainly to the cerebral cortex, the
hippocampus, and basal ganglia

4. • In the mid-1950s, the discovery that the pronounced
behavioral effects of reserpine are accompanied by a
profound decrease in brain 5-HT led to the proposal
that serotonin may function as a neurotransmitter in
the mammalian CNS.
• 5-hydroxytryptamine (5-HT)
• The highest concentrations were found in GI mucosa,
followed by platelets and the CNS
• Cell bodies are found in raphe nucleus, pons, and
medulla (part of the reticular formation)
• Projections are mainly to the cerebral cortex, the
hippocampus, and basal ganglia

5. • Numerous synthetic or naturally occurring congeners of 5-HT have
pharmacological activity.
• Many of the N- and O-methylated indoleamines, such as N,N-dimethyl-
tryptamine, are hallucinogens , they have long been considered candidates
for endogenous psychotomimetic substances, potentially responsible for
some psychotic behaviors.
• Another close relative of 5-HT, melatonin (5-methoxy-N-acetyltryptamine),
is formed by sequential N-acetylation and O-methylation.
• principal indoleamine in the pineal gland, where it may be said to constitute
a pigment of the imagination. Its synthesis is controlled by external factors
including environmental light.
• Melatonin induces pigment lightening in skin cells and suppresses ovarian
functions; it also serves a role in regulating biological rhythms and shows
promise in the treatment of jet lag and other sleep disturbances.

6. • Tryptophan is actively transported into the brain by a
carrier protein that also transports other large neutral and
branched-chain amino acids.
• Competition
• Tryptophan hydroxylase, a mixed-function oxidase that
requires molecular O2 and a reduced pteridine cofactor for
activity, is the rate-limiting enzyme in the synthetic
pathway.
• A brain-specific isoform of tryptophan hydroxylase (TPH2)
is entirely responsible for the synthesis of brain 5-HT
• Brain tryptophan hydroxylase is not generally saturated
with substrate; consequently, the concentration of
tryptophan in the brain influences the synthesis of 5-HT.

7. • 5-HT, is accumulated in secretory granules by a vesicular
monoamine transporter (VMAT2) a nonspecific amine carrier
• Exocytosis
• In the nervous system, the action of released 5-HT is terminated via
neuronal uptake by a specific 5-HT transporter.
• 5-HT transporter (SERT ) on Axon and plt membrain an especific
transporter
• Most 5-HT receptors, especially the 5-HT2C receptor, can activate
G-proteins independently of agonists, a property known as
constitutive activity
• Plays a role in many behaviours:
– Regulation of mood
– Control of eating, sleep, arousal
– Regulation of pain
• Involved in higher cognition and emotion

8. 1. Ionotropic receptor: contains a binding site and and
ion channel
Binding of neurotransmitter directly opens channel
2. Metabotopic receptor: contains binding site for
neurotransmitter.
• Activates an enzyme that begins a series of events
that opens up a channel
• Release of a G-protein that is coupled to the receptor
• Second messenger: G-proteins convey messages to
other molecules that in turn produce other activating
chemicals

9. PSY4080 6.0D9 Neurotransmitter Function

10. • 5-HT1 Receptors.
• The 5-HT1-receptor subfamily consists of five members, all of which
preferentially couple to Gi/o and inhibit adenylyl cyclase.
• The 5-HT1A, 5-HT1B, and 5-HT1D receptor subtypes also activate a
receptor-operated K+ channel and inhibit a voltage-gated Ca2+ channel, a
common property of receptors coupled to the pertussis toxin–sensitive
Gi/Go family.
• The 5-HT1A receptor is found in the raphe nuclei of the brainstem, where
it functions as an inhibitory, somatodendritic autoreceptor on cell bodies
of serotonergic neurons
• Another 5-HT1-receptor subtype, the 5-HT1D/1B receptor, functions as
an autoreceptor on axon terminals, inhibiting 5-HT release, 5-HT1B.
• 5-HT1D receptors, abundantly expressed in the substantia nigra and basal
ganglia, regulate the firing rate of DA-containing cells and the release of
DA at axonal terminals.

11. • The 5-HT1A receptor is found in the raphe nuclei
of the brainstem, where it functions as an
inhibitory, somatodendritic autoreceptor on cell
bodies of serotonergic neurons
• Another 5-HT1-receptor subtype, the 5-HT1D/1B
receptor, functions as an autoreceptor on axon
terminals, inhibiting 5-HT release, 5-HT1B.
• 5-HT1D receptors, abundantly expressed in the
substantia nigra and basal ganglia, regulate the
firing rate of DA-containing cells and the release
of DA at axonal terminals.

12. PSY4080 6.0D12 Neurotransmitter Function

13. PSY4080 6.0D13 Neurotransmitter Function

14. PSY4080 6.0D14 Neurotransmitter Function

15. Electrophysiological
properties
PSY4080 6.0D15 Neurotransmitter Function