KOMUNIKASI ANTAR SEL :

SECOND MESSENGER &

PROTEIN-G

Nur Faidah
P062171604
Sub Pokok Bahasan

Second Messenger

Protein G dan reseptornya

G protein-coupled receptors
yang meregulasi kanal ion
Second Messenger
 Introduction
 Second messengers are intracellular molecules that change in
concentration in response to environmental signals. That change
in concentration conveys information inside the cell.
 Second messengers participate in many signal-transduction
pathways.
 Because second messengers are generated by enzymes or by the
opening of ion channels, their concentrations can be tremendously
amplified compared with the signals that lead to their generation.
 Specialized proteins sense the concentrations of these second
messengers and continue the flow of information along signal-
transduction pathways.
 Some particularly important second messengers are cyclic AMP
(cAMP) and cyclic GMP (cGMP), calcium ion, inositol 1,4,5-
trisphosphate (IP3), and diacylglycerol
 Second Messenger
 Cyclic AMP is a second messenger that is capable of diffusing to
other sites within the cell.
 The synthesis of cyclic AMP follows the binding of a first
messenger a hormone or other ligand to a receptor at the outer
surface of the cell.
 Whereas the first messenger binds exclusively to a single receptor
species, the second messenger often stimulates a variety of
cellular activities.
 As a result, second messengers enable cells to mount a large‐scale,
coordinated response following stimulation by a single
extracellular ligand.
G protein–coupled receptors
 Introduction
 the most numerous class of receptors are the G protein–coupled
receptors (GPCRs).

 In humans, GPCRs are used to detect and respond to many

different types of signals, including neurotransmitters, hormones
involved in glycogen and fat metabolism, and even photons of
light.

 Many GPCRs are found primarily in cells of the central nervous

system and are used in neuronal signaling

 GPCRs are of immense medical importance, as approximately 30

percent of all drugs used in humans are agonists or antagonists of
specific GPCRs or groups of closely related GPCRs.
 all GPCR signal transduction pathways share the
following common elements:
(1) A receptor that contains seven membrane-spanning α helices;
(2) A heterotrimeric G protein, which functions as a receptor-
activated switch by cycling between active and inactive forms;

(3) A membrane-bound effector protein; and

(4) Proteins that participate in desensitization of the signaling
pathway. Second messengers are also a part of many GPCR
pathways. GPCR pathways usually have short-term effects in the
cell by quickly modifying existing proteins, either enzymes or
ion channels.
All G Protein–Coupled Receptors Share the Same
Basic Structure

General structure of G protein–coupled receptors. All receptors

of this type have the same orientation in the membrane and
contain seven transmembrane α-helical regions (H1–H7), four
extracellular segments (E1–E4), and four cytosolic segments
(C1–C4).
 Ligand-Activated G Protein–Coupled Receptors
Catalyze Exchange of GTP for GDP on the α Subunit
of a Heterotrimeric G Protein
G Protein–Coupled Receptors
That Regulate Ion Channels
 Introduction
 One of the simplest cellular responses to a signal is the open- ing or
closing of ion channels that are essential for trans- mission of nerve
impulses.

 Nerve impulses are essential to the sensory perception of

environmental stimuli such as light and odors, to the transmission of
information to and from the brain, and to the stimulation of muscle
movement.

 During transmission of nerve impulses, the opening and closing of ion

channels causes changes in the membrane potential.

 Many neurotransmitter receptors are ligand-gated ion channels, which

open in response to the binding of a ligand. Such receptors include
some types of glutamate, serotonin, and acetylcholine receptors,
including the acetylcholine receptor found at nerve-muscle synapses.
 Many neurotransmitter receptors are G protein–
coupled receptors whose effector proteins are Na+ or
K+ channels.
 Neurotransmitter binding to these receptors causes the
associated ion channel to open or close, leading to
changes in the membrane potential.
 Still other neurotransmitter receptors, as well as
odorant receptors in the nose and photoreceptors in
the eye, are G protein–coupled receptors that indirectly
modulate the activity of ion channels via the action of
second messengers.
 Acetylcholine Receptors in the Heart Muscle
Activate a G Protein That Opens K+ Channels
 Muscarinic acetylcholine receptors are a type of GPCR
found in cardiac muscle.
 When activated, these receptors slow the rate of heart
muscle contraction.
 This type of acetylcholine receptor is coupled to a Gαi
protein, and ligand binding leads to the opening of an
associated K+ channel (the effector protein) in the plasma
membrane
 The subsequent efflux of K+ ions from the cytosol causes an
increase in the magnitude of the usual inside-negative
potential across the plasma membrane that lasts for several
seconds.
 This state of the membrane, called the hyperpolarized
state, reduces the frequency of muscle contraction.
 the signal from activated mus- carinic
acetylcholine receptors is transduced to
the effector channel protein by the
released Gβγ subunit, rather than by
Gαi∙GTP.

 That Gβγ directly activates the K+

channel was demonstrated by patch-
clamping experiments, which can
measure ion flow through one or a few
ion channels in a small patch of
membrane

 When purified Gβγ (but not Gαi∙GTP)

protein was added to the cytosolic face
of a patch of heart muscle plasma
membrane, K+ channels opened
immediately, even in the absence of
acetylcholine or other
neurotransmitters—clearly indicating
that it is the Gβγ protein that is
responsible for opening the effector K+
channels.
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