3. OPIOID PEPTIDES
Opioid peptides produced in the body act as neuro-modulators that modify the
actions of other neuro-transmitters in the central nervous system.
By altering the electrical properties of their target neurons, there by making these
neurons more difficult to excite, opioid peptides can influence the release of
various neurotransmitters.
As a result of this modulation, opioid peptides can—among other functions—
induce pain relief and euphoria as well as affect certain behaviors, including
alcohol consumption
4. OPIATES VS OPIOIDE PEPTIDES
Opiates, sometimes known as narcotics,
are a type of drug that act as depressants
on the central nervous system (CNS).
Opiates come from opium, which can be
produced naturally from poppy plants.
Opioids are chemically
synthesized opiate-like drugs.
• They are synthesized
endogenously within our body.
5. ROLE OF OPIOID PEPTIDES
Produce same effects as the chemicals known as classic alkaloid opiates, which
include morphine and heroin.
◼ Function both as hormones and as neuromodulators :
1. As hormones, they are secreted into the circulation by the producing glands and
are delivered to a variety of distant target tissues where they induce a response.
2. As neuromodulators, they are produced and secreted by nerve cells (i.e.
neurons) and act in the brain and spinal cord to modulate the actions of other
neurotransmitters.
◼ Through these two mechanisms, opioid peptides produce many effects, ranging
from preventing diarrhea to inducing euphoria and pain relief (i.e.,analgesia).
6. CLASSIFICATION OF OPIOID PEPTIDES
There are two types –
1.Endogenous opioid peptide-Endogenous opioid peptides are small molecules that are naturally
produced in the central nervous system (CNS) and in various glands throughout the body, such
as the pituitary and adrenal glands.
• Endorphins, Enkephalins , Dynorphins and Endomorphins are together referred to as
endogenous opioid peptides.
Derived from distinctive precursor proteins which undergo complex cleavages as well as
modifications and are encoded by their corresponding gene codes
• Inactive precursors are distributed in the brain and the periphery and give rise to active
peptides by undergoing structural modifications.
7. 1. Endorphins
Endorphins are formed by the pituitary gland, hypothalamus, many parts of brain
and nervous system in the conditions of tiring workout, exhilaration as well as
pain.
Endorphins are of four different types i.e., alpha, beta, gamma and sigma having
16–31 different types of amino acids in their molecules.
Beta-endorphins (in the pituitary gland as well as hypothalamus) stand out as the
most powerful opioid peptide and play an important role as neuromodulators as
well as hormones.
These help to alleviate body pain, stress and anxiety and at the same time cause
the feeling of elation and excitement, power and better control of oneself
8. 2. Enkephalins
Are present in the brain, pituitary gland, gastrointestinal tract as well as the
kidneys and are released in response to some harmful stimuli.
These are further of two types i.e., Metenkephalins and the other one is Leu-
enkephalins
9. 3. Dynorphins
Are produced at multiple sites in the body such as different parts of brain and
spinal cord.
Based upon their site of production, these peptides perform various physiological
functions such as patterning of electrical activity of neurons, inhibition of oxytocin
secretion, controlling appetite, maintaining homeostasis, modulating pain
response, controlling weight etc.
10. 4. Endomorphins
Are of two types i.e., Endomorphin 1 and Endomorphin 2
Abundantly present in the CNS i.e., brain and spinal cord.
Play a significant role in realization of pain and stress, feeling of reward, arousal
etc.
Several conditions like electrical stimulation of the central grey matter,
acupuncture and other non-stressful conditions causes a release of endogenous
opioid peptides resulting into an increase of peptides in the cerebrospinal fluid
and blood plasma
11. .Exogenous
Exogenous opioid substances are called exorphins, as opposed to endorphines.
Exorphins include opioid food peptides like Gluten exorphin and opioid food
peptides and are mostly contained in cereals and animal milk. They mimic the actions
of endorphines because they bind to the same opioid receptors in the brain.
These are the most common exorphins:
• Casomorphin (from casein found in milk of mammals, including cows)
• Gluten exorphin (from gluten found in cereals wheat, rye, barley)
• Gliadorphin/gluteomorphin (from gluten found in cereals wheat, rye, barley)
• Soymorphin-5 (from soybean)
• Rubiscolin (from spinach)
12. OPIOID PEPTIDES PRODUCTION
Many peptides with opioidlike effects have been found in the CNS and in peripheral tissues.
These peptides fall into three categories— enkephalins, endorphins, and dynorphins—that are
derived from three distinct precursor molecules.
The active, functional opioid peptides are generated from their precursors by enzymes called
peptidases, which cut these precursor molecules into smaller entities. The peptides are then
modified further during posttranslational processing, which can include the addition of various
chemical groups to the peptides (e.g., sugar molecules [i.e., glycosylation], acetyl groups [i.e.,
acetylation], phosphate groups [i.e., phosphorylation], or methyl groups [i.e., methylation]).
These modifications can alter the peptides’ biological activities. Because the processing of opioid
peptides from larger precursor molecules is very selective, the opioid-peptide profiles can vary
among different tissue types.
13. MECHANISM OF ACTION OF OPIOID
PEPTIDES
Once released from the neurons, opioid peptides act through opioid receptors on their
target neurons to transmit messages that primarily inhibit secondary systems, such as
pain perception.
In addition, opioid peptides can induce the following effects:
• Decrease respiration
• Stimulate or depress cardiovascular functioning,
• Decrease the movement of the muscles of the GI tract
• Decrease susceptibility to seizures
• Induce euphoria
• Affect certain behaviors, such as the consumption of food and alcohol
14. Fig .The seven transmembrane structure of opioid G-protein-coupled receptors.
Activation by opioid receptor ligands leads to initiation of intracellular
transduction pathways that include stimulation of potassium efflux, inhibition of
VSCCs, and inhibition of adenylyl cyclase.
15. G-protein-coupled receptors, such as those for opioids, have no direct link with effector proteins;
instead the message is relayed via a G-protein.
Both classical opioid receptors (MOP/KOP/DOP) and the nonclassical NOP opioid receptor couple
to inhibitory G-proteins.
Activation of opioid receptors, e.g. MOP with morphine leads to:
(i) closing of voltage sensitive Ca2+ channels (VSCC);
(ii) stimulation of potassium efflux leading to hyperpolarization;
(iii) reduced cyclic adenosine monophosphate (cAMP) production via inhibition of adenylyl cyclase.
Overall, this results in reduced neuronal cell excitability leading to a reduction in transmission of
nerve impulses along with inhibition of neurotransmitter release
16.
17. OPIOID RECEPTORS
Receptors are proteins which are, by far the most important drug targets in
medicine.
The opioid receptors belong to family of G-protein coupled receptors. Morphine
and other opioids exert their actions by interacting with specific receptors present
on neurons in the CNS and in peripheral tissues.
The interaction of drug with receptor was analogous a "lock and "key".
Agonist: An agent who activates a receptors to produce an effect to that of the
physiological signal molecules.
Antagonist: An agent which prevents the action of an agent on receptor. or the
subsequent response but does not have any effect of its own.
18. TYPES OF OPIOID RECEPTORS
The opioid receptors are mainly classified as three types:
A) Mu(u) receptors
B) Kappa (K) receptors•
C) Delta (8) receptors.
D) Nociception/Orphan receptor
19.
20. TYPE A: Mu Receptors
The mu receptors are characterized by its high affinity for morphine. The
endogenous ligand for mu receptors-peptides called endomorphins1and 2, have
only recently been found in mammalian brain.
Endomorphine-1 and endomorphine-2 are endogenous opioid peptide with high
degree of selectivity for mu receptors.
The opioid drugs are morphine, codeine, ethyl morphine, methadone, tramadol,
fentanyl.
The two subtypes of mu receptors have been proposed:
a) Mu 1.receptors
b)Mu 2.receptors
21. Type 2: Kappa (k) receptors
The Kappa receptor defined by its highly affinity for Ketocyclazocine and
dynorphin.
Ethyleketazocine and bremazocine are two compounds used in early studies to
investigate kappa receptors.
The two subtypes of kappa receptors have been proposed:-
1.kappa(k1) receptor
2.kappap(k3) receptor
22. TYPE C: DELTA RECEPTOR
In delta receptors the endomorphine have lesss elective.
Generally Etorphine, Cyclozacine, levorphinol, are the agonist involved in delta
receptors.
The delta receptors have less serious side effects as compare to mu receptors.
the two subtypes of delta recepptors have been proposed:
1.Delta() receptor
2.Delta() receptor
23. SITE OF ACTION OF OPIOID PEPTIDES
1. Anatomical Distribution in the Brain.
Not all opioid peptide-containing neurons are located in the same brain areas.
For example, neurons that contain enkephalins have been found in many different
brain regions, suggesting that these peptides are involved in many physiological
functions.
For example, enkephalins mediate pain perception by acting in the spinal cord
and in the periaqueductal gray (PAG) region of the brain
24. The distribution of neurons containing the other two types of opioid peptides—
beta-endorphin and the dynorphins—is not as diffuse as that of the neurons
containing enkephalins.
1. Neurons that contain beta-endorphin are found predominately in the
hypothalamus and in a region of the brain stem (i.e., the nucleus of the solitary tract).
2. The dynorphin-containing neurons are located primarily in the hypothalamus.
25. 2. Anatomical Distribution in the
Periphery
All three types of opioid peptides (i.e., enkephalins, endorphins, and dynorphins)
are found in the pituitary and adrenal glands.
Although many stimuli can induce the pituitary to release opioid peptides into
the circulation, the precise function of these peptides in their peripheral target
tissues is not well understood.
Opioid peptides have been found in many organ tissues throughout the body,
including the heart, pancreas, placenta, kidneys, and gastrointestinal organs
26. CONCLUSION
Opioids are chemically synthesized opiate-like
drugs.
Opioid Peptides are basically neuromodulators.
They are of 4 types : endorphins, enkephalins, dynorphins and endomorphins.
Opioid receptors interact with particular opioid peptides to initiate a particular
chain of bio chemical events to bring out a response.
Receptors are of 4 types as well, namely Mu, Kappa, Delta, and Nocireceptor
