Endorphin is the body's natural analgesic hormone. It is produced when the body experiences physical or emotional stress and binds to the same opioid receptors as exogenous opioids like morphine. There are different types of endorphin including beta-endorphin, which is one of the most potent analgesics. Endorphin production varies between individuals and functions to reduce both physical and emotional pain by increasing pleasure and suppressing pain signals in the brain. Understanding the endogenous opioid system and how endorphin interacts with receptors provides insights into developing future analgesic treatments.
1. ENDORPHIN : A NATURAL ANALGESIC AND
PLEASANT HORMONE
BY: NEHA JAIN
M.Phil.Bioscience
2. 2
Endorphins "endogenous morphine"
Beta-endorphin the best in pain relief
Endorphins production is hereditary, and due to this, its
production level varies from one person to another.
High concentrations of endorphins in the brain
produce a sense of euphoria, enhance pleasure, and
suppress pain, both emotionally and physically.
Low concentrations of endorphins in the brain people
feel anxious and they are also more aware of pain.
3. OVERVIEW OF PRESENTATION
1) History
2) What is Endorphin
3) Types of Endorphin
4) Control of Secretion
5) Transport and distribution
6) Receptors of endorphin
7) Binding: endorphin and receptor
8) Function as analgesic
9) Mode of action
10)Can we get endorphin ?
11)Abnormalities of endorphin receptors
12)Receptors used by exogenous opioid (morphine)
13)what is drug addiction ?
14)Can Methadone Fix to endorphin Receptors?
15)Future of endorphin’s and other’s receptors
4. HISTORY
In 1970’s that many research allowed us to understand how the exogenous
opioid drugs work by studying the “endogenous opioid system”.
In 1973, H. Solomon Snyder and Johns hopkins discovered the
“endogenous opioid system”. Researchers also determined the
existence of opiate binding sites in the brain through the use of radioligand
binding assays.
In 1974, Rabi Simantov and Solomon H. Snyder isolated endogenous opioid
from the brain of a calf , and term is given "endorphin" (i.e. Endogenous
morphine).
In 1975, an endogenous opiate-like factor called enkephalin was found and
shortly after this two more classes of endogenous opiate peptides were
isolated, the dynophorins and the “endorphins”.
5. WHAT IS ENDORPHIN?
A peptide hormone named Endorphin produced in
the brain and anterior pituitary.
Endorphin inhibits pain perception. It is popularly
called Body’s natural analgesic or opiate.
Endorphin is produced at the time of physical or
emotional stress, such as labor of child birth.
Endorphin binds to the same receptors that binds
exogenous opiates.
“Endorphin Affect Your Mood And
Emotions And May Be Responsible
For Your Body Feeling Pleasure
Even Euphoria For Your Body Feeling Pleasure”
6. alpha (α) endorphin -
beta (β) endorphin Most powerful
gamma (γ) endorphin -
sigma (σ) endorphin -
TYPES OF ENDORPHIN
Human body produces at least 20 different
endorphins ( benefits and uses are investigating)
Special types are as follows:
(made all by 16 to 31 amino acids )
7. β -ENDORPHIN
• β -Endorphin is peptide hormones (consist of chains of
amino acids) ----NH2 / NH3 + COOH
• β -Endorphin is a 31 amino acid polypeptide
• SEQUENCE: Ac - Tyr - Gly - Gly - Phe - Met - Thr - Ser
- Glu - Lys - Ser - Gln - Thr - Pro - Leu - Val - Thr - Leu -
Phe - Lys - Asn - Ala - Ile - Ile - Lys - Asn - Ala – His -
Lys - Lys - Gly - Gln – OH
• β-endorphin is released by pituitary
(into blood ) and hypothalamus ( into the
spinal cord and brain )
• β-endorphin is a cleavage product of pro-
opiomelanocortin (POMC)
8. Hypothalamus
Corticotropin releasing factor
(CRF)
Anterior Pituitary
Pro-Opiomelanocortin
(POMC)
Endorphin Hormone
(EP)
Central Nervous
System
Environmental
Cue
“Stressor”
( pain)
•Step 1: Cue perceived by
CNS
•Step 2: Signal sent to
hypothalamus (in
brain)
•Step 3: Hypothalamus
secretes CRF
(peptide), travels to
pituitary
•Step 4: CRF causes protein
pro-Opiomelanocortin
hormone (POMC) to be
cleaved, releases Beta
lipotropin
•Step 5: lipotropin gets convert
into Endorphin.
•Step 6: Endorphin binds to
the nerve fiber.
Brain
Beta-lipotropin
10. RECEPTORS OF ENDORPHIN
• All of the endorphins
bind to the opioid
receptors in the brain.
• These analgesia-
producing receptors are
located in your brain,
spinal cord, and other
nerve endings.
Mu ( ) Receptor Analgesic (most
important )
Delta( ) Receptor Analgesic
(predominantly )
Kappa () Receptor Analgesic (hyper-
analgesic )
11. TRANSPORT AND DISTRIBUTION
β-endorphin is released by :
1. Pituitary (into blood ) and
2. Hypothalamus ( into the spinal
cord and brain )
Beta endorphin containing nerve
fibres spread widely from
neurones in the hypothalamus,
to make inhibitory contacts with
target neurones to reduce pain.
Free hormones are rapidly eliminated
from circulation through
kidney or liver.
Hypothalamus
12. An Easy Way to Think of Receptors
and Endorphins binding
• Is to think of the substance
as a key and the receptor as
a lock.
• When the substance binds to
the receptor it opens the
lock.
• This in turn sends another
signal or causes the release
of a substance.
• When a lot of signals are sent a function
happens like the release of a hormone.
13. BINDING OF ENDORPHIN & RECEPTOR
Portion of molecule
Where ligand binds
Is called binding site.
If the molecule
Is a receptor (like in a
cell membrane) the
binding site is called
receptor site.
The purpose of binding
to target tissue is to
elicit a response by
the target cell.
17. MODE OF ACTION
The mu receptor is the strongest binding site of the body’s
natural pain killer, the class of opioid peptides called the
endorphin.
The mu receptor is a G-protein linked receptor. When
endorphin binds to the delta receptor is induces a
conformational change that causes the activation of a
specific G-protein.
This G-protein inhibits the membrane bound enzyme
adenylate cyclase and prevents the synthesis of cAMP.
The transmission of the pain signal requires cAMP to act
as a secondary messenger, and so inhibition of this enzyme
blocks the signal .
(Pain-relieving effect by blocking the release of substance P)
Adenylcyclase
Endorphin
ATP cAMP AMP
18. 18
Calcium channels
closed
Potassium channels open
K+
AC
Gi
[cAMP]
Calciumentry
blocked [Ca2+]
Decreased release of
neurotransmitters
Endorphin Receptor
2. Directaction on K channels (alpha &
beta subunit)
Net effects:
K+ conductance hyperpolarize neurons
Ca+ conductance neurotransmitter release
1. Couple to Gi &
Go protein
(neuronal
excitability)
Pain reduced
MODE OF ACTION
19. CAN WE GET ENDORPHIN ?
Yes we can get : BY
Chili Runner’s high
Exercise Music
Laughing
Meditation
Acupuncture
20. ABNORMALITIES OF ENDORPHIN
RECEPTORS
However with some people :
When the lock (receptor) is damaged.
No matter how much Endorphins may be near
the receptor because it does not function right
the lock can not be opened.
By Genetics/Birth Defect
A person can be born with defective receptors.
This can make an individual more susceptible to
addiction
By Exogenous drug
And using opiates - not for pain - but when the
brain is flooded over and over again – the
receptors stop working normally.
21. ENDORPHIN RECEPTORS USED BY
EXOGENOUS OPIOID (Morphine)
Morphine
Carbon
Hydrogen
Nitrogen
Sulfur
Oxygen
Natural
endorphin
(a) Structures of endorphin and morphine.
Natural
endorphin
Endorphin
receptors
Morphine
Brain cell
(b) Binding to endorphin receptors
22. ENDORPHIN MORPHINE
Endogenous opioid. Exogenous opioid
Powerful analgesic 18 to 500
times than morphine
(Β-endorphin is 80 times)
Less analgesic than
endorphin
similar Molecular structure &
Different chemical properties.
It also
Non-addictive Addictive
Does not cause addiction Side-effects : euphoria/
dysphoria, constipation,
respiratory depression,
nausea/ vomiting etc.
Receptors are :
mu, kappa, delta
Receptors are :
mu, kappa, sigma
Metabolized quickly Metabolized slowly
HOW DOES POTENCY DIFFER?
23. WHAT IS DRUG ADDICTION ?
In the normal course Opiate
Receptors and Endorphins are
kept in balance with one
another.
When the brain is flooded with
exogenous opiates, (heroin a
morphine derivative) it mimic of
endorphins so system gets
confused.
It thinks it is making too many
endorphins and shuts that
down, But it still has all this
excess (heroin) and thinks that
it also needs to make more
receptors.
Heroin addiction
24. What Happens Next….
• As more Opiate Receptors are
made you need more heroin to
get the same effect so you use
more.
• And more receptors are made
to accommodate the extra
what the brain thinks is
endorphins.
• For decreasing this effect-
You need more substance to
get the same effect.
25. Can Methadone Fix to
endorphin Receptors?
• Methadone does normalize the damage
caused by drug use(heroin).
• Synthetic. Long half-life Used to reduce
withdrawal symptoms of heroin addicts
• And there is some evidence that for
persons who have not used drugs very
long that methadone will stop the damage
they are doing and over time can
normalize the system.
• But this is a small minority – 30%.
72-84 hr (Slow excretion)
Half-life > 24 hr
Half-life > 12 hr
Methadone
Heroin
2 hr ( fast excretion)
26. FUTURE OF ENDORPHIN’S AND
OTHER’S RECEPTORS
• The future of Opioid Analgesics seems to be linked to the
study of the Kappa Receptor. The kappa receptor induces
analgesia without the dangerous and unwanted side effects
that the mu and delta receptors are associated with.
• However there are not any selectively strong agonists to this
receptor as of now.
• Another area of research important to the future of opioid
analgesics is the study of the endogenous opioid peptides.
27. FUTURE OF ENDORPHIN’S AND
OTHER’S RECEPTORS
• Because these peptides are endogenous, on metabolic
degradation (unlike opiates) they break down to amino
acids. Hence, the metabolites are nontoxic and to not cause
kidney and liver damage
• Also, because they are made from amino acid residues, a
large number of analogs can be synthesized from a few
basic building blocks and simple modifications may be
attempted to develop analogs with a desired biological
effect .
28. SUMMARY
• Endorphin is best analgesic endogenous
opioid.
• For future research endorphin receptors
are very important.
Heroin one thousand times more powerful and potent than morphine. It also used endorphin receptor site For binding.It caused drug addiction more than others.
