Transcript Chemical messengers 2007

Chemical messengers
intro
• Chemical messengers include
neurotransmitters (short distance) and
hormones (long distance)
• Whatever the messenger, the cell must
have a receptor to detect the signal’s
presence.
• The binding of the messenger to the
receptor causes signal transduction.
Hormone messengers
neurotransmitters
SEROTONIN
Receptor locations
• The receptor is a
membrane protein (or
glycoprotein).
– They have to be on the
cell membrane because
most messengers won’t
pass through the lipid
bilayer.
– some messengers can
pass through the
membrane, these
molecules have
receptors inside the cell.
Specificity
• Although a chemical messenger might
come into contact with many different
cells, it only affects some cells and not
others.
• Usually only certain cell types have the
receptor required to receive a specific
chemical messenger.
• When different cells have different receptors for
the same messenger, each cell will respond
differently to the messenger.
Effect of the messenger
• The messenger acts as a switch that
causes the cell’s response.
– Think of a switch for a light or a radio, the
same messenger can cause different
responses in different cell types.
– A single cell may have many different
receptors for many different messengers.
Saturation
• a cell’s response to a messenger
increases as the concentration of the
messenger increases.
– the number of receptors occupied by
messenger molecules increases.
Competition
• Different messenger molecules that are
very similar in structure compete with each
other for a receptor.
Example of competition
• Let’s say a doctor wants to interfere with
the action of a messenger, they can
prescribe a molecule that is similar to the
messenger that will bind to its receptor.
– This blocks the messenger, but doesn’t
stimulate the cell’s response.
– These drugs are called antagonists.
• Beta Blockers are used to treat high blood
pressure.
• Antihistamines
agonists
• Some competitors stimulate the cell’s
response when they bind with the
receptor.
• These drugs are called agonists.
– Ephedrine (a nasal decongestant) is used to
bind to receptors that cause muscles in blood
vessels to constrict (like epinephrine does)
• This causes fewer sniffles.
Regulation of receptors
• The number of receptors a cell has can be
increased or decreased in some cells.
• Down Regulation- desensitizes
– when a high concentration of messengers is
maintained for a long time outside the cell, the
total number of receptors for that messenger
may decrease or down-regulate.
Up regulation
• Up Regulation-supersensitive
– Cells exposed to very low concentrations of
messengers for long periods of time will
produce more receptors.
• Example
– Cut the nerves to a muscle so that no more
neurotransmitter is released to make them
contract,
– a few days later add a small amount of
neurotransmitter to the muscle, it will contract.
Controlling response
• Up regulation and Down regulation are
possible because receptor molecules are
continuously being broken down and
made by the cell.
Diseases affect receptors
• Some diseases can affect the number of
receptors available on the cell surface.
– This can increase or decrease the cell’s
response to a specific messenger.
– Example
• Myasthenia gravis is caused by the destruction of
skeletal muscle receptors for acetylcholine that
causes muscle contraction.
• Result: muscle weakness, later paralysis.
Receptor activation
• The combination of messenger with
receptor causes a change in the shape of
the receptor.
• This is known as receptor activation.
• This is always the first step in the cell’s
response to the messenger.
Cell responses to the messenger
• Responses to the messenger can include
changes in:
– The permeability, transport properties or
electrical state of the membrane
– The cell’s metabolism
– What the cell secretes
– The cell’s rate of division (mitosis)
– The cell’s contractile (contracting or relaxing)
activity
Changes in cell proteins cause
responses to the messenger
• Nerve cells generate an electrical signal as a
result of neurotransmitters changing the shape
of ion channels (membrane proteins) that allow
Na+ to diffuse into the cell.
• The rate of glucose secretion from the liver is
increased when epinephrine causes increases in
the number of enzymes involved in glucose
synthesis.
• Muscle contraction results from the altered
shape of contractile proteins which is caused by
a chemical messenger.
Some definitions
• first messengers.
– The chemical messengers that bind to the receptor
• Second messengers
– are generated in the cytoplasm as a result of the
receptor being activated by the first messenger OR
– molecules that enter the cell.
– move throughout the cell to communicate from the
cell membrane to the proteins inside the cell that do
the work.
• Protein kinase
– any enzyme that phosphorylates other proteins by
transferring a phosphate to them from ATP.
– The protein (enzyme) that receives the phosphate
changes it shape and carries out its function.
Signal transduction pathway
• The sequence of events
between receptor
activation and cell
response are called
signal transduction
pathways.
• The “signal” is the
receptor activation.
• “transduction” is the
process by which the
stimulus is transformed
into a response.
Different receptors produce
different cell responses
• Each of the
four kinds of
receptors is
responsible for
one or more of
the cell’s
responses.
Receptor type
Ion channel
Protein Kinase
JAK
G protein
Cell response
Ion channel
receptor
• Activation of the
receptor by the first
messenger causes
the channel to open.
– The opening results
in an increase in the
net diffusion of the
ion across the
membrane.
– Remember that ion
channels are specific
to one type of ion
(Na+, K+, Ca+).
Protein Kinases
receptors that act as enzymes
• These receptors are usually
involved in cell differentiation
or cell division.
• Receptors that act as
enzymes are all protein
kinases (except for one).
– The binding of the messenger
to the receptor changes the
receptor shape and activates
the enzyme part located inside
the membrane.
– This cause
autophosphorylation of the
receptor molecule
continued
• Then the cytoplasmic
side of the receptor acts
as a “docking” site for
other proteins.
– These proteins that joined
with the receptor then bind
with other proteins in a
cascade
– In each cascade, at some
point, they all involve
activation of proteins in the
cytoplasm by
phosphorylation.
• The end result of all these
cascades is the activation
of molecules that control
the response of the cell to
the messenger.
Receptors that interact with
cytoplasmic JAK kinases
• JAK stands for Just Another
Kinase.
• These receptors are usually
involved in the production of
proteins for export.
• Like receptors that act as
enzymes, these receptors
also have enzyme activity.
– the receptor does not house the
enzyme, instead other enzymes
bind to the receptor when it
binds to the messenger.
JAK kinases
phosphorylate
proteins
• The binding of the receptor to the messenger
causes the JAK kinase to be activated.
• These JAK kinases phosphorylate proteins involved
in transcription.
• The result of these cascades is the production of
new proteins.
Receptors that interact with G
proteins
• the largest
category of
receptors
– There are
hundreds of
different kinds.
– Bound to the
receptor inside the
membrane is a set
of G proteins.
• The binding of the first messenger to the receptor cause the
receptor to change shape.
• This causes part of the G protein to bind to GTP
• The part that binds to GTP then breaks off the rest of the
protein and binds to another membrane protein, either an ion
channel or enzyme.
A summary of receptor types and
cell responses
Receptor type
Cell response
Ion channel
Membrane permeability;
contractility
Protein Kinase
Mitosis rate
JAK
Protein secretion
G protein
Membrane permeability;
contractility; metabolism