Chemical messengers

intro• Chemical messengers include

neurotransmitters (very short distance), paracrine agents (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

Paracrine Agents

• Growth factors• Blood clotting

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 in a cell can be increased or decreased.

• 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.• Type II diabetes is a result of down regulation of

insulin receptors.

Up regulation• Up Regulation-supersensitive

– Cells exposed to very low concentrations of messengers for long periods of time will produce more receptors.

• Example– Just prior to birth, cells in the uterus become

more sensitive to the effects of the hormone oxytocin which causes uterine contractions.

Controlling response

• Up regulation and Down regulation are possible because receptor molecules are continuously being broken down and made by the cell.

• Overstimulation by too many messengers can cause a cell to …

• Understimulation by not enough messengers can cause a cell to …

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

What Cell response are we stimulating

• When neurotransmitter bind to a receptor, they will cause ion channels to open. These channels can then cause the neuron to generate an action potential.

• Epinepherine binds to liver cells and causes them to break down glycogen to glucose. The glucose is then released to fuel your escape from a dangerous situation.

• The paracrine agent TGF1-beta can cause a cell to undergo mitosis or apoptosis.

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. – They 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.

Signal amplification

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 Cell response

Ion channel

Protein (Tyrosine) KinaseJAK

G protein

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 (Tyrosine) Kinasesreceptors 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, secretion