By binding to a new nuclear-associated receptor, opioid
growth factor (OGF), also known by its chemical name
[Met5]-enkephalin, promotes cellular homeostasis.
Serum OGF levels are high in diabetic individuals.
In the animal model, opioid receptor antagonists like
naltrexone (NTX) alleviate many of the consequences of
diabetes
4. Introduction
▪ First indication of endogenous opioids in brain extracts was
published in 1975 by John Hughes and Hans Kosterlitz.
▪ These opioids might prevent the release of acetylcholine
from guinea pig ileum neurons.
Compounds that they first isolated were termed
enkephalins.
Met-encephalins and leu-encephalins (Cullen, J. M., &
Cascella, M, 2020)
7. Mechanism of Action:
▪ There are three primary kinds of opioid receptors: mu, which
is mostly expressed in the central nervous system.
▪ Delta, which is equally expressed in the spinal nerve and
spinal cord, and kappa, which is mainly expressed in the
spinal cord.
▪ Despite its discovery in 1994, the fourth class of opioid
receptors known as nociceptin is not regarded as belonging to
the previously stated tripartite group, which is often known as
the classical opioid receptors.
8. Enkephalins have the highest affinity for the delta-opioid
receptor, followed by the mu-opioid receptor, and exhibit
low affinity for the kappa-opioid receptor.
Opioid receptors are in the family of G-protein coupled
receptors recognized by their seven membrane-spanning
motifs with approximately 60% sequence homology.
When analyzing sequence similarity, their extracellular
domains—which control their selectivity—show between
34 and 49%.
The first step in signal transduction is the dissociation of
the Gα and Gβγ subunits due to ligand binding.
9. Cellular hyperpolarization is brought on by the Gα
subunit's direct interaction with inward rectifying
potassium channels.
In addition, the Gα subunit suppresses the activity of
adenylyl cyclase, which lowers the synthesis of cAMP
and, consequently, the cAMP-dependent Ca2+ influx.
Through direct binding to several kinds of Ca2+ channels,
the Gβγ further decreases calcium flow.
Because the endogenous opioid system is widely
distributed throughout the human neurological system and
body, dysregulation of this system can have ramifications
for a wide range of disease conditions (Cullen, J. M., &
Cascella, M, 2020)
11. Up-regulation
Fig. 1.2: Upregulation of enkephalin
https://images.app.goo.gl/fx54fzCz8g
W21ooo9
Depressive
Disorder
Chronic
restraint
stress
(CRS)
Increased
by 28%
causes
emotional and
physiological
changes
Depressive
Disorder
12. Downregulation
Fig. 1.3: Downregulation of
Enkephalin
https://images.app.goo.gl/Jwey3j8cHA
hFNxMh6
Im-
mobiliza
tion
hypothala
mic
ppENK
Repeated
observation
DAMGO
13. Enkephalin and Scar healing:
Distinct neuropeptide receptors have been detected in distinct
forms of scar tissue, according to a recent clinical
investigation.
The alanine scan approach was utilized to produce enkephalin
derivatives from L-ENK.
A full-thickness skin defect in a mouse model, examined the
speed at which the wound healed.
It was followed the injection of L-ENK, and then examined its
impact on the formation of scars (Kim et.,al 2023)
14. Advancements
Polycystic Ovary Syndrome:
Enkephalins influence the
etiology of obesity, maturation of
follicles, and the secretion of
insulin.
Naltrexone and naloxone are two
opioid antagonists (Garg et
al.,2023)
Fig. 1.4: Enkephalin and PCOS
https://images.app.goo.gl/VUDhWMa5B
N6rpAsKA
15. Crohn’s Disease:
▪ Every year, 5 to 20.2/100,000 cases
▪ Teenagers between the ages of 10 and 19 have been
diagnosed with 25% of instances.
▪ The two most typical signs of CD are diarrhea and
stomach pain.
▪ When it comes to treating moderate to severe pain,
opioids are thought to be the best option.
▪ serious adverse effects such as physical dependence,
respiratory center depression, and suppression of
gastrointestinal motility.
16. Crohn’s Disease:
Endogenous opioids or endo-opioids,
which are endorphins, dynorphins,
and enkephalins.
They are in charge of inhibiting
intestinal motility and gastric
emptying in the gut.
ε-opioid receptors (MORs),
δ-opioid receptors (DORs), and
κ-opioid receptors (KORs) are the three different types
(Martyniak et.,al 2023)
Fig.1.5: Crohn’s disease
https://images.app.goo.gl/LKyXo
SXTNnmqMpTW8
17. Diabetes
By binding to a new nuclear-associated receptor, opioid
growth factor (OGF), also known by its chemical name
[Met5]-enkephalin, promotes cellular homeostasis.
Serum OGF levels are high in diabetic individuals.
In the animal model, opioid receptor antagonists like
naltrexone (NTX) alleviate many of the consequences of
diabetes (Purushothaman et.,al 2021)
18. References
Cullen, J. M., & Cascella, M. (2020). Physiology,
enkephalin.
Wu, S., Ning, K., Wang, Y., Zhang, L., & Liu, J. (2023). Up-
regulation of BDNF/TrkB signaling by δ opioid receptor
agonist SNC80 modulates depressive-like behaviors in
chronic restraint-stressed mice. European Journal of
Pharmacology, 942, 175532.
Martyniak, A., Wędrychowicz, A., & Tomasik, P. J. (2023).
Endogenous opioids in Crohn’s disease. Biomedicines, 11(7),
2037.
19. Kim, S. E., Kim, Y. J., & Cheon, Y. W. (2023). Role of
enkephalin derivative in promoting wound healing and scar
remodeling via increased epidermal growth factor in a mouse
model. Archives of Aesthetic Plastic Surgery, 29(1), 1-7.
Purushothaman, I., Zagon, I. S., Sassani, J. W., &
McLaughlin, P. J. (2021). Ocular surface complications in
diabetes: The interrelationship between insulin and
enkephalin. Biochemical Pharmacology, 192, 114712
