Physiology2 - Sheet#8 - Dr.Loai Alzgoul - Done By: Mais Al-Reem Al-Housani
Norepinephrine (α and β family receptors)
It's a slow neurotransmitter
(neuromodulator)
*The cell bodies of neurons that release
norepinephrine are located in an area in the
brain stem which is called "nucleus locus
coeruleus", while their axons are distributed
throughout the brain and the body .
*Amines synapses are alike, but dopamine
and norepinephrine differ in the response of
their specific transporters to cocaine. While
the amphetamine affects both (stop it) and
they share the same enzyme of degradation
( mono amino oxidase ).
* Norepinephrine performs its actions on the target cell by binding to and activating . The target
cell expression of different types of receptors determines the ultimate cellular effect, and thus
norepinephrine has different actions on different cell types.
*norepinphrine is highly responsive to
external stimuli. what do we mean by stimuli?
Example:
Stimuli (a sudden loud voice )
norepinphrine in the brain
Activation of locus coeruleus
attention
release of
If locus coeruleus is sensitive to any small stimuli, it'll release more epinephrine than
needed and this would keep the patient aware with extra attention causing him a
stress disorder, such as: anxiety.
Physiology2 - Sheet#8 - Dr.Loai Alzgoul - Done By: Mais Al-Reem Al-Housani
Norepinephrine enhances :
1- learning and memory (remember :posterior part of cortex which have α2
receptors is responsible for attention and memory)
2- attention
* increasing norepinephrine:
stress and anxiety disorder ( excessive feelings and fears )
ADHD disease (attention deficiency hyperactivity disorder ).
3- Mood regulation  Hypofunction of pathwayDepression
( remember : frontal cortex, which contains β1 receptors, is responsible for the
personality and mood).
* decreasing norepinephrine:
bad mood and may cause depression
* we give norepinephrine agonist for patients who suffer from depression or
memory defect and to be more selective we target β1 receptors .
4- sweep/wake cycle.
Serotonin
* serotonin is synthesized from the amino acid "tryptophan" .
Tryptophan is an essential amino acid, we get it from diet since we can't produce it
in our bodies. This means that the synthesis of serotonin depends on the presence of
tryptophan so this is the rate limiting step .
* serotonin is releases from region in the brain stem that
is called ( dorsal raphe /raphe nucleus/ median raphe ).
Physiology2 - Sheet#8 - Dr.Loai Alzgoul - Done By: Mais Al-Reem Al-Housani
* serotonin as other neurotransmitter goes to all regions in the brain and it is the
denser neuromodulator in the brain .
* serotonin has 17 receptor and they discovered more in the last few years .these
receptors are divided into families , each of them operate in a certain way .
Serotonin Receptors
NOTE : 5-HT (5-hydroxy tryptophan) is another expression for serotonin
serotonin receptors' families
5-HT3
Function
Works through ionic channels
5-HT4, 5-HT6 , 5-HT7
excitatory (stimulates cAMP)
5-HT1, 5-HT5
Inhibitory (inhibits cAMP)
5-HT2
Excitatory (stimulates PLC (phospholipase-C) )
*There are 3 special serotonin receptors and considered as auto receptors:
Auto receptors
5-HT1A
5-HT1B
5-HT2B
Function
"inhibition" it is like D2 receptor
"inhibition" it is like D2 receptor
Increase PLC
increase Calcium
" inhibition"
REMEMPER: auto receptors are receptors located on presynaptic nerve cell
membranes or on the serotonin neuron itself, to regulate the release of the
neurotransmitter . example: kainate receptor, D2 receptor .
Physiology2 - Sheet#8 - Dr.Loai Alzgoul - Done By: Mais Al-Reem Al-Housani
* serotonin works through 17 receptors and controls most of the functions of the
brain : mood, sleep, sexuality, impulsivity, aggression, stress, drug abuse. It's related
to many diseases and disorders : Depression, Schizophrenia, OCD( obsessive
compulsive disorder) , Eating Disorders, Autism .
*These drugs work on serotonin receptors: Antipsychotics, Anxiolytics, Antiemetics,
Anti-migraine.
Neuropeptides:
*Neuropeptides are peptides released by neurons as intercellular messengers
(neurotransmitters).
* Although there're way more different types of neuoropeptides than classical
neurotransmitter, neuropeptides are available in a less concentration than the
classical neurotransmitters yet widely distributed. However, their potency is
effective; lower concentration and longer effect, and they can do just about
everything.
* neuropeptides are synthesized in the cell body and in a less time than that needed
for the synthesis of classical neurotransmitters.
*May co-localize with other classical transmitters in same neuron (EXAMPLE:
serotonin neuron that has vesicles of a neuropeptid).
*All neuropeptide receptors are G-protein linked receptors because they only
work through second messenger receptors.
We will discuss in brief only one family from neuropeptides which is
*(opioids)*
opioids
Endorphin
Enkephalin
1)Enkephalin : (works through δ receptor)
Function: analgesia by blocking the pain before it is relayed to the brain
Physiology2 - Sheet#8 - Dr.Loai Alzgoul - Done By: Mais Al-Reem Al-Housani
*enkephalin are released from brain stem (mid brain ) and
enters this pathway :
Mid brain (periaqueductal gray)
raphe nucleus( stimulate
serotonin)
serotonin enters spinal cord
serotonin
stimulate another enkephalin neurons there
block the
pain sensation (ALS pathway ) in the spinal cord .
NOTE: enkephalin inhibits pre and post synapses(in the spinal
cord) :
inhibition for presynapse
neurotransmitters
decreasing the release of
inhibition for postsynapse
potential .
decreasing membrane
*conclusion : to decrease the pain we have two choices either by stimulating
"enkephalin" or increasing "serotonin" in the cases of severe pain .
2)Endorphin:
*in the past , people discovered morphine as a pain relief . After that they
discovered its receptor in the body which they called µ receptors (morphine
receptors ) . BUT since we have special receptors for morphine then there must be
something similar to morphine structure in our bodies. That was" Endorphin".
*Endorphins suppress the pain, and change the way in which people perceive pain
(you feel the pain, but instead of that pleasure is enhanced)
(so Endorphins inhibit pain or changes the emotion aspect of pain).
Nontraditional neurotransmitters:
1)Nitric oxide (NO):
*NO is a diffusible bioactive gas produced from arginine by
nitric oxide synthase. It is produced on the spot and it's not
stored in vesicles: neuron produces NO and it exits the
neuron directly .
* nitric oxide synthase is responsible for manufacturing NO
BDNF
Non traditional
Nitric oxide
Physiology2 - Sheet#8 - Dr.Loai Alzgoul - Done By: Mais Al-Reem Al-Housani
In the brain, NO acts as a neuromodulator to control behavioral activity,
influence memory formation, and intensify responses to painful stimuli
May be responsible for glutamate induced neurotoxicity:
*neurons that work through NO synthase will produce NO when calcium ions
increase , because this enzyme is calcium dependent so it's related to glutamate
(NMDA receptors ) and many of its functions.
*remember that NMDA receptors are related to stroke disorder; NO increases stroke
disorder .
*on stroke disorder all neurons die, not only glutamate neurons :
Glutamate neurons release calcium ions
glutamate neurons die by apoptosis
Increasing calcium will result in releasing
NO (that makes GABA neurons die as well)
2)"BDNF" brain derived neurotrophic factor:
BDNF is a neurotransmitter, and a growth factor which works through receptors (TRK
receptors) that either stimulate the cell survival and growth and differentiation or
the death of the cell .
*It's considered as nontraditional
neurotransmitter because in some cases it
is released from postsynaptic neuron to
presynaptic neuron (so the BDNF
receptor is on presynaptic terminus).
Example :
Activation of glutamate neuron
action potential
release of glutamate
activation of postsynaptic membrane
Release serotonin at the terminal
Release BDNF to presynaptic neuron
The terminus allows the passage
of the neurotransmitter with its
receptor driving them back to the
cell body and then it's translated
into cell survival info.