* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Chemical messengers 2007
Survey
Document related concepts
Tyrosine kinase wikipedia , lookup
Killer-cell immunoglobulin-like receptor wikipedia , lookup
Purinergic signalling wikipedia , lookup
VLDL receptor wikipedia , lookup
Biochemical cascade wikipedia , lookup
Lipid signaling wikipedia , lookup
Leukotriene B4 receptor 2 wikipedia , lookup
G protein–coupled receptor wikipedia , lookup
Paracrine signalling wikipedia , lookup
Toll-like receptor wikipedia , lookup
Transcript
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