Cell Reports,
Год журнала:
2024,
Номер
43(5), С. 114164 - 114164
Опубликована: Апрель 27, 2024
Opioid
receptors
are
therapeutically
important
G
protein-coupled
(GPCRs)
with
diverse
neuromodulatory
effects.
The
functional
consequences
of
opioid
receptor
activation
known
to
depend
on
location
in
the
plasma
membrane,
but
mechanisms
mediating
selective
localization
any
particular
membrane
domain
remain
elusive.
Here,
we
demonstrate
targeting
mu
(MOR)
primary
cilium,
a
discrete
microdomain
somatic
both
vivo
and
cultured
cells.
We
further
show
that
ciliary
is
specific
MORs,
requires
17-residue
sequence
unique
MOR
cytoplasmic
tail,
additionally
Tubby-like
protein
3
(TULP3)
adaptor
protein.
Our
results
reveal
potential
for
undergo
cilium.
propose
mediated
through
an
elaboration
recycling
pathway,
directed
by
C-terminal
cis
requiring
TULP3
trans.
Annual Review of Neuroscience,
Год журнала:
2022,
Номер
45(1), С. 223 - 247
Опубликована: Март 9, 2022
Breathing
is
a
vital
rhythmic
motor
behavior
with
surprisingly
broad
influence
on
the
brain
and
body.
The
apparent
simplicity
of
breathing
belies
complex
neural
control
system,
central
pattern
generator
(bCPG),
that
exhibits
diverse
operational
modes
to
regulate
gas
exchange
coordinate
an
array
behaviors.
In
this
review,
we
focus
selected
advances
in
our
understanding
bCPG.
At
core
bCPG
preBötzinger
(preBötC),
which
drives
inspiratory
rhythm
via
unexpectedly
sophisticated
emergent
mechanism.
Synchronization
dynamics
underlying
preBötC
rhythmogenesis
imbue
system
robustness
lability.
These
are
modulated
by
inputs
from
throughout
generate
rhythmic,
patterned
activity
widely
distributed.
connectivity
emerging
literature
support
link
between
breathing,
emotion,
cognition
becoming
experimentally
tractable.
bring
great
potential
for
elucidating
function
dysfunction
other
mammalian
circuits.
Pharmacology & Therapeutics,
Год журнала:
2021,
Номер
233, С. 108019 - 108019
Опубликована: Окт. 11, 2021
Overdose
deaths
are
often
viewed
as
the
leading
edge
of
opioid
epidemic
which
has
gripped
United
States
over
past
two
decades
(Skolnick,
2018a).
This
emphasis
is
perhaps
unsurprising
because
overdose
both
number-one
cause
death
for
individuals
between
25
and
64
years
old
(Dezfulian
et
al.,
2021)
a
significant
contributor
to
decline
in
average
lifespan
(Dowell
2017).
Exacerbated
by
COVID
19
pandemic,
it
was
estimated
there
were
93,400
drug
during
12
months
ending
December
2020,
with
more
than
69,000
(that
is,
>74%)
these
fatalities
attributed
(Ahmad
2021).
However,
focus
on
mortality
statistics
2021;
Shover
2020)
tends
obscure
broader
medical
impact
nonfatal
overdose.
Analyses
multiple
databases
indicate
that
each
opioid-induced
fatality,
6.4
8.4
non-fatal
overdoses,
exacting
burden
individual
society.
Over
7-8
years,
been
an
alarming
increase
misuse
synthetic
opioids
("synthetics"),
primarily
fentanyl
related
piperidine-based
analogs.
Within
2-3
structurally
unrelated
class
high
potency
synthetics,
benzimidazoles
exemplified
etonitazene
isotonitazene
("iso"),
have
also
appeared
illicit
markets
(Thompson,
2020;
Ujvary
al.
In
80%
fatal
overdoses
now
involve
synthetics
The
unique
physicochemical
pharmacological
properties
described
this
review
responsible
morbidity
associated
their
well
widespread
availability.
dramatic
referred
"3rd
wave"
(Pardo
2019;
Volkow
Blanco,
epidemic.
Among
consequences
resulting
from
potent
need
higher
doses
competitive
antagonist,
naloxone,
reverse
development
effective
reversal
agents
such
those
essential
component
tripartite
strategy
(Volkow
Collins,
2017)
reduce
biopsychosocial
"synthetic
era".
Journal of Neurophysiology,
Год журнала:
2021,
Номер
125(5), С. 1899 - 1919
Опубликована: Апрель 7, 2021
Opioid-induced
respiratory
depression
(OIRD)
represents
the
primary
cause
of
death
associated
with
therapeutic
and
recreational
opioid
use.
Within
United
States,
rate
from
abuse
since
early
1990s
has
grown
disproportionally,
prompting
classification
as
a
nationwide
“epidemic.”
Since
this
time,
we
have
begun
to
unravel
many
fundamental
cellular
systems-level
mechanisms
opioid-related
death.
However,
factors
such
individual
vulnerability,
neuromodulatory
compensation,
redundancy
effects
across
central
peripheral
nervous
systems
created
barrier
concise,
integrative
view
OIRD.
review,
bring
together
multiple
perspectives
in
field
OIRD
create
an
overarching
viewpoint
what
know,
where
essential
topic
research
going
forward
into
future.
British Journal of Pharmacology,
Год журнала:
2021,
Номер
180(7), С. 813 - 828
Опубликована: Июнь 5, 2021
Respiratory
depression
is
the
proximal
cause
of
death
in
opioid
overdose,
yet
mechanisms
underlying
this
potentially
fatal
outcome
are
not
well
understood.
The
goal
review
to
provide
a
comprehensive
understanding
pharmacological
opioid‐induced
respiratory
depression,
which
could
lead
improved
therapeutic
options
counter
as
other
detrimental
effects
opioids
on
breathing.
development
tolerance
system
also
discussed,
differences
degree
caused
by
various
agonists.
Finally,
potential
future
agents
aimed
at
reversing
or
avoiding
through
non‐opioid
receptor
targets
and
certain
advantages
over
naloxone.
By
providing
an
overview
network,
will
benefit
research
countering
depression.
LINKED
ARTICLES
This
article
part
themed
issue
Advances
Opioid
Pharmacology
Time
Epidemic.
To
view
articles
section
visit
http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc
Proceedings of the National Academy of Sciences,
Год журнала:
2021,
Номер
118(23)
Опубликована: Май 31, 2021
Significance
Opioid-induced
respiratory
depression
(OIRD)
is
the
direct
cause
of
death
from
opioid
overdose,
which
accounts
for
current
global
crisis.
Here,
we
report
that
neurons
expressing
μ-opioid
receptors
in
lateral
parabrachial
nucleus
pontine
group
are
necessary
and
sufficient
pathogenesis
OIRD.
Activating
these
through
endogenous
or
artificial
G
protein–coupled
receptor
signaling
pathways
rescues
OIRD
intact
mice,
suggesting
its
therapeutic
utility
patients.
The Journal of Comparative Neurology,
Год журнала:
2021,
Номер
529(11), С. 2911 - 2957
Опубликована: Март 14, 2021
The
parabrachial
nucleus
(PB)
is
composed
of
glutamatergic
neurons
at
the
midbrain-hindbrain
junction.
These
form
many
subpopulations,
one
which
expresses
Calca,
encodes
neuropeptide
calcitonin
gene-related
peptide
(CGRP).
This
Calca-expressing
subpopulation
has
been
implicated
in
a
variety
homeostatic
functions,
but
overall
distribution
this
region
remains
unclear.
Also,
while
previous
studies
rats
and
mice
have
identified
output
projections
from
CGRP-immunoreactive
or
neurons,
we
lack
comprehensive
understanding
their
efferent
projections.
We
began
by
identifying
with
Calca
mRNA
CGRP
immunoreactivity
around
PB,
including
populations
locus
coeruleus
motor
trigeminal
nucleus.
PB
prominently
express
mu
opioid
receptor
(Oprm1)
are
distinct
neighboring
that
Foxp2
Pdyn.
Next,
used
Cre-dependent
anterograde
tracing
synaptophysin-mCherry
to
map
these
neurons.
heavily
target
subregions
amygdala,
bed
stria
terminalis,
basal
forebrain,
thalamic
intralaminar
ventral
posterior
parvicellular
nuclei,
hindbrain,
different
patterns
depending
on
injection
site
location
within
region.
Retrograde
axonal
revealed
previously
unreported
hindbrain
arise
rostral-ventral
subset
CGRP/Calca
Finally,
show
those
information
provides
detailed
neuroanatomical
framework
for
interpreting
experimental
work
involving
CGRP/Calca-expressing
action
The Journal of Biochemistry,
Год журнала:
2024,
Номер
175(4), С. 367 - 376
Опубликована: Фев. 2, 2024
Abstract
Biased
signaling,
also
known
as
functional
selectivity,
has
emerged
an
important
concept
in
drug
development
targeting
G-protein-coupled
receptors
(GPCRs).
Drugs
that
provoke
biased
signaling
are
expected
to
offer
opportunity
for
enhanced
therapeutic
effectiveness
with
minimized
side
effects.
Opioid
analgesics,
whilst
exerting
potent
pain-relieving
effects,
have
become
a
social
problem
owing
their
serious
For
the
of
safer
pain
medications,
there
been
extensive
exploration
agonists
distinct
balance
G-protein
and
β-arrestin
(βarr)
signaling.
Recently,
several
approaches
based
on
protein–protein
interactions
developed
precisely
evaluate
individual
signal
pathways,
paving
way
comprehensive
analysis
signals.
In
this
review,
we
describe
overview
bias
opioid
receptors,
especially
μ-opioid
receptor
(MOR),
how
GPCR
field.
We
discuss
future
directions
rational
through
integration
diverse
datasets.