Biological reviews/Biological reviews of the Cambridge Philosophical Society,
Journal Year:
2013,
Volume and Issue:
88(3), P. 645 - 668
Published: Jan. 29, 2013
Abstract
Cyclic
AMP
(
cAMP
)
plays
a
key
regulatory
role
in
most
types
of
cells;
however,
the
pathways
controlled
by
may
present
important
differences
between
organisms
and
tissues
within
specific
organism.
Changes
levels
are
caused
multiple
triggers,
affecting
adenylyl
cyclases,
enzymes
that
synthesize
.
Adenylyl
cyclases
form
large
diverse
family
including
soluble
forms
others
with
one
or
more
transmembrane
domains.
Regulatory
mechanisms
for
involve
either
interaction
proteins,
as
happens
Escherichia
coli
yeasts,
calcium
bicarbonate
ions,
occurs
mammalian
cells.
The
can
be
regulated
variety
among
which
α
subunit
βγ
complex
from
G
proteins
coupled
to
membrane
receptors
prominent.
also
activity
phosphodiesterases,
hydrolyze
Phosphodiesterases
,
cGMP
calcium‐calmodulin
phosphorylation
different
protein
kinases.
Regulation
through
depends
on
its
binding
proximal
targets,
this
turn
causing
changes
distal
targets.
Specifically,
subunits
‐dependent
kinases
PKAs
affects
substrates
PKA
exchange
directly
activated
Epac
regulates
small
GTPases
transcription
factors
such
receptor
CRP
virulence
factor
regulator
Vfr
modifies
rate
certain
genes,
while
ion
channels
modulates
their
directly.
Further
studies
signalling
will
have
implications,
not
only
advancing
fundamental
knowledge
but
identifying
targets
development
new
therapeutic
agents.
Circulation Research,
Journal Year:
2010,
Volume and Issue:
106(4), P. 659 - 673
Published: March 4, 2010
Abstract:
Ion
channels
on
the
surface
membrane
of
sinoatrial
nodal
pacemaker
cells
(SANCs)
are
proximal
cause
an
action
potential.
Each
individual
channel
type
has
been
thoroughly
characterized
under
voltage
clamp,
and
ensemble
ion
currents
reconstructed
in
silico
generates
rhythmic
potentials.
Thus,
this
can
be
envisioned
as
a
“membrane
clock”
(M
clock).
Localized
subsarcolemmal
Ca
2+
releases
generated
by
sarcoplasmic
reticulum
via
ryanodine
receptors
during
late
diastolic
depolarization
referred
to
intracellular
“Ca
clock,”
because
their
spontaneous
occurrence
is
periodic
clamp
or
detergent-permeabilized
SANCs,
well.
In
spontaneously
firing
M
clocks
do
not
operate
isolation
but
work
together
numerous
interactions
modulated
voltage,
,
protein
kinase
A
CaMKII-dependent
phosphorylation.
Through
these
interactions,
2
subsystem
become
mutually
entrained
form
robust,
stable,
coupled-clock
system
that
drives
normal
cardiac
cell
automaticity.
G
protein–coupled
signaling
creates
flexibility,
ie,
effects
changes
potential
rate,
impacting
very
same
factors
regulate
robust
basal
function.
This
review
examines
evidence
forms
basis
concept
SANCs.
The Annual Review of Pharmacology and Toxicology,
Journal Year:
2007,
Volume and Issue:
48(1), P. 359 - 391
Published: Oct. 3, 2007
Caveolae,
a
subset
of
membrane
(lipid)
rafts,
are
flask-like
invaginations
the
plasma
that
contain
caveolin
proteins,
which
serve
as
organizing
centers
for
cellular
signal
transduction.
Caveolins
(-1,
-2,
and
-3)
have
cytoplasmic
N
C
termini,
palmitolylation
sites,
scaffolding
domain
facilitates
interaction
organization
signaling
molecules
so
to
help
provide
coordinated
efficient
Such
components
include
upstream
entities
(e.g.,
G
protein-coupled
receptors
(GPCRs),
receptor
tyrosine
kinases,
steroid
hormone
receptors)
downstream
heterotrimeric
low-molecular-weight
effector
enzymes,
ion
channels).
Diseases
associated
with
aberrant
may
result
in
altered
localization
or
expression
proteins
caveolae.
Caveolin-knockout
mice
numerous
abnormalities,
some
reflect
impact
total
body
knockout
throughout
life
span.
This
review
provides
general
overview
caveolins
caveolae,
localize
role
caveolae/caveolin
cardiac
pulmonary
pathophysiology,
pharmacologic
implications
caveolar
molecules,
possibility
caveolae
might
therapeutic
target.
Neurosignals,
Journal Year:
2008,
Volume and Issue:
17(1), P. 5 - 22
Published: Oct. 27, 2008
Cyclic
AMP
is
a
universal
second
messenger,
produced
by
family
of
adenylyl
cyclase
(AC)
enzymes.
The
last
three
decades
have
brought
wealth
new
information
about
the
regulation
cyclic
production
ACs.
Nine
hormone-sensitive,
membrane-bound
AC
isoforms
been
identified
in
addition
to
tenth
isoform
that
lacks
membrane
spans
and
more
closely
resembles
cyanobacterial
New
model
systems
for
purifying
characterizing
catalytic
domains
led
crystal
structure
these
mapping
numerous
interaction
sites.
However,
big
hurdles
remain
unraveling
roles
individual
their
physiological
systems.
In
this
review
we
explore
latest
on
knockout
overexpression
studies
better
understand
G
protein
ACs
brain,
olfactory
bulb,
heart.
Physiological Reviews,
Journal Year:
2012,
Volume and Issue:
92(1), P. 39 - 74
Published: Jan. 1, 2012
Fluid
and
HCO
3
−
secretion
is
a
vital
function
of
all
epithelia
required
for
the
survival
tissue.
Aberrant
fluid
associated
with
many
epithelial
diseases,
such
as
cystic
fibrosis,
pancreatitis,
Sjögren's
syndrome,
other
inflammatory
autoimmune
diseases.
Significant
progress
has
been
made
over
last
20
years
in
our
understanding
secretion,
particular
by
secretory
glands.
glands
two-step
process.
Acinar
cells
secrete
isotonic
which
major
salt
NaCl.
Subsequently,
duct
modifies
volume
electrolyte
composition
to
absorb
Cl
.
The
relative
secreted
acinar
modification
fluids
varies
among
meet
their
physiological
functions.
In
pancreas,
small
amount
NaCl-rich
fluid,
while
absorbs
secretes
bulk
pancreatic
juice.
appears
be
driven
active
secretion.
salivary
glands,
saliva
that
contains
high
concentrations
Na
+
both
K
this
review,
we
focus
on
molecular
mechanism
pancreas
highlight
similarities
fundamental
mechanisms
cell
functions,
point
out
differences
gland-specific
secretions.
Cold Spring Harbor Perspectives in Biology,
Journal Year:
2010,
Volume and Issue:
2(12), P. a004010 - a004010
Published: Oct. 27, 2010
Colin
W.
Taylor
and
Stephen
C.
Tovey
Department
of
Pharmacology,
University
Cambridge,
Tennis
Court
Road,
CB2
1PD,
United
Kingdom
Correspondence:
cwt1000{at}cam.ac.uk
Pharmacological Reviews,
Journal Year:
2013,
Volume and Issue:
65(3), P. 1010 - 1052
Published: June 17, 2013
The
EP4
prostanoid
receptor
is
one
of
four
subtypes
for
prostaglandin
E2.
It
belongs
to
the
family
G
protein–coupled
receptors.
was
originally
identified,
similar
EP2
as
a
Gsα-coupled,
adenylyl
cyclase–stimulating
receptor.
signaling
plays
variety
roles
through
cAMP
effectors,
i.e.,
protein
kinase
A
and
exchange
activated
by
cAMP.
However,
emerging
evidence
from
studies
using
pharmacological
approaches
genetically
modified
mice
suggests
that
EP4,
unlike
EP2,
can
also
be
coupled
Giα,
phosphatidylinositol
3-kinase,
β-arrestin,
or
β-catenin.
These
pathways
constitute
unique
widely
distributed
in
body
thus
various
physiologic
pathophysiologic
roles.
In
particular,
closely
related
carcinogenesis,
cardiac
hypertrophy,
vasodilation,
vascular
remodeling,
bone
gastrointestinal
homeostasis,
renal
function,
female
reproductive
function.
addition
classic
anti-inflammatory
action
on
mononuclear
cells
T
cells,
recent
has
shown
contributes
proinflammatory
well.
aim
this
review
present
current
findings
biologic
functions
we
will
discuss
its
diversity
standpoint
EP4-mediated
signaling.