Theme 3 - intercellular signalling Flashcards
what is intercellular signalling?
extracellular signalling between cells
what is intracellular signalling?
occurs within cells
give four reasons why cells need to communicate
communicate with neighbour cells, adapt metabolism and nutritional requirements to nutritional state of the body, induce or stop growth/cell division, respond to danger signals
what can bone marrow stem cells become?
all components of the blood
when new cells are needed, what must stem cells do?
upregulate proliferation by the right amount and differentiate to the desired cell type
what are the five basic steps of intercellular signalling?
synthesis and release of the signal molecule, transport of signal molecule to target cell, detection of the signal by a receptor on the target cell, change in cellular behaviour due to activated of the receptor, removal of the signal
two ways a signal can be removed to terminate cellular response?
removal of ligand binding the target receptor or removal of the receptor itself
name four types intercellular signals with examples
proteins (Interferon and insulin), peptides (glucagon and growth hormone), small chemicals (steroids made from cholesterol and amino acid metabolites), dissolved gases (nitric oxide)
name two steroids made from cholesterol that can be used as intercellular signals
estradiol and cortisol
name two amino acid metabolites that can be used as intercellular signals
adrenaline and histamine
what three factors must be in place for a cell to respond to a signal?
ligand present, responding cell has relevant receptor, receptor is correctly coupled to an intracellular signalling pathway
what determines what receptors are present on a cell and to what level they are expressed?
gene expression and levels can be determined by the cellular environment
give two reasons why a cell may not respond to a signal even though it has the correct receptor?
the cell may have already been exposed to the signal or there may be an interacting signal that affects the receptor activity
why are most receptors found at the cell surface?
many signalling molecules cant cross the lipid membrane as they are too large or too hydrophilic
what are the three main types of receptor?
ion channels. GPCRs and enzyme linked receptors
what are three effects of receptor activation and how long do they take?
altered protein function eg contraction (seconds), secretion (mins), protein synthesis (12-24 hours)
what two classes of molecule can pass the cell membrane and bind intracellular receptors?
small molecules (nitric oxide) and hydrophobic molecules (steroid hormones and thyroxin)
what type of receptors are found intracellularly?
nuclear receptors - whole ligand receptor complex moves to the nucleus to exert its effects
what happens to a cell if it is not receiving any signals?
it will undergo apoptosis
give an example of two cells responding differently to the same molecule
adrenaline - causes smooth muscle contraction in gut blood vessels but relaxation in blood vessels of smooth muscle cells supplying muscles
why can one molecule (adrenaline) exert different effects on different tissues?
presence of different adrenergic receptors - alpha adrenergic in the gut causing contraction and beta adrenergic in the skeletal muscle to cause relaxation
what receptors does adrenaline bind to in the gut and what does this cause?
binds to alpha adrenergic receptors and this causes contraction
what receptors does adrenaline bind to in the skeletal muscle and what does this cause?
binds to beta adrenergic receptors and this causes relaxation
what type of receptors are adrenergic receptors?
GPCRs
what ligand binds to muscarinic M1 and M2 receptors?
acetylcholine
what type of muscarinic receptors does Ach bind on salivary glands and what is the effect?
Ach binds M1 muscarinic receptors in the salivary glands and this causes secretion
what type of muscarinic receptors does Ach bind on heart pacemaker cells and what is the effect?
Ach binds the M2 muscarinic receptors in the heart and causes decreased rate of firing
what ion channel can Ach activate and where is this found?
Ach can activate nicotinic receptors eg Na+/K+ ATPase on skeletal muscle
what effect does Ach have on skeletal muscle
contraction via binding to nicotinic sodium potassium ATPase
how can one signal have many different effects?
depends on what receptors are present and what signalling pathways they activate
name a long range (m) signal
endocrine
name four short range (micrometer) signals
paracrine, neuronal, autocrine and juxtacrine
how does a hormone exert its effects?
released from an endocrine gland into the bloodstream, bathes all body cells in the hormone but only some cells have the right receptor to respond - usually affect gene expression
what happens when you eat food and blood sugar increases?
beta cells in IOL in the pancreases recognise increase in blood glucose and releases insulin
what does insulin do when released due to increased blood glucose?
activates liver cells, skeletal muscle and adipocytes to take up the excess glucose
what cells take up excess glucose?
liver cells, skeletal muscle cells and adipocytes
what cell types sense when blood glucose is too low and how do they respond?
alpha cells in the IOL of the pancreas respond by releasing glucagon
what does glucagon do?
released when blood glucose is too low and signals to the liver and adipocytes to release glucose
what can signalling errors result in?
type I or type II diabetes
what happens in type I diabetes
autoimmune and early onset - immune system destroys beta cells in IOL so insulin isn’t made
what happens in type II diabetes
absent or decreased response to insulin by liver cells and adipocytes
name one way glucose levels can be controlled in type II diabetes
with diet
what receptor does cortisol bind and where is it found?
binds the glucocorticoid receptor which is found intracellularly
what effects can the cortisol-GC receptor complex have on gene expression?
acts as a transcription factor to activate or suppress gene expression
name two effects of cortisol
drive production of glucose or be anti-inflammatory by regulating T cells
name three synthetic hormone drugs that activate the glucocorticoid receptor
hydrocortisone, prenisolone, dexmethasone
name three conditions where synthetic steroids can be used as drugs
autoimmune - psoriasis/ulcerative colitis, allergy - urticaria and asthma
what drug can be given in asthma
dexmethasone
what is paracrine signalling?
release of signalling molecules that diffuse locally to neighbour cells only
name three types of molecule that can be paracrine signals
proteins, amino acid derivatives and dissolved gases (NO)
name two proteins that act in a paracrine manner
cytokines (immune response) or platelet derived growth factor (stimulates cell proliferation)
name an amino acid derivative that acts in a paracrine manner
histamine - released from mast cells and induces local inflammation - derivative of histidine
what amino acid is nitric oxide a derivative of and what effects does it have
Argenine and it causes vasodilation by relaxing smooth muscle
how is NO made from argenine?
act activates IP3 in endothelial cells in blood vessels which causes calcium release which activates NO synthase and argenine makes NO
what is target enzyme does NO bind to and where is this found?
guanylate cyclase and is found in the cytoplasm
what does guanylate cyclase do once bound to NO?
converts GTP to cGMP and relaxes smooth muscle and increases blood flow through the vessel
how long is the half life of cGMP and why?
short half life (10 seconds) as it is quickly hydrolysed by phosphodiesterase
how does PDE hydrolyse cGMP?
cleaves the cyclic bond
where can interfering with PDE be clinically useful and why?
cardiovascular disease - use a small molecule to inhibit PDE and therefore increase the half life of NO leading to prolonged smooth muscle relaxation
what other effect was the PDE inhibitor developed by Pfizer found to have besides in CAD?
anti impotence
what drugs target PDE 5 and where is it expressed?
viagra - PDE 5 is expressed in the corpus caveosum
what would inhibiting PDE do to cAMP?
increase its half life by preventing its hydrolysis
give one clinical use of NO
treatment of angina (nitroglycerin)
what are the symptoms of angina?
pain radiating down the left arm due to decreased blood flow to the heart
how does nitroglycerin treat angina?
nitroglycerin tablet or patch is quickly converted to NO which leads to vasodilation and therefore increased blood flow to coronary arteries
what type of paracrine signalling only happens at NMJs?
neuronal signalling
what does adrenaline do when acting as a neurotransmitter?
regulates attentiveness and mental focus
what does adrenaline do when acting as a hormone?
redirects blood to the muscles and increases conversion of glycogen to glucose
give one example of where Ach can be released
in the gut to innervate muscle cells
what is serotonin derived from and give an examples of what it is implicated in
derived from tryptophan and can modulate mood
what is dopamine derived from and give an examples of what it is implicated in
derived from tyrosine and involved in fine tuning of motion
what is autocrine signalling?
when cells secrete signals that bind their own receptors and generate a change in their own behaviour - short distance
what kind of feedback loop is autocrine signalling an example of?
positive feedback
Give an example of a positive feedback loop mediated by autocrine signalling
TNF cytokine production from monocytes which feeds back onto the TNF receptors on the cell to amplify the signal and increasing further cytokine production
what molecule is implicated in cancer when autocrine signalling goes wrong?
EGF - uncontrolled release of EGF by cells which acts on the cells causing it to grow and divide out of control - tumour
what is juxtacrine signalling?
contact dependent signalling where no signalling molecule is released - happens between immediate neighbours via membrane bound molecules
what are two examples of juxtacrine signalling?
gap junctions and contact dependent ligand receptor binding
how do gap junctions mediate juxtacrine signalling?
cells line up and form a channel between them that allows transfer of cytoplasmic contents eg ions, nucleotides and sugars
how does contact dependent ligand receptor binding mediate juxtacrine signalling?
direct cell communication or interactions with the ECM
what causes gap junctions to open or close?
phosphorylation
what subunits are gap junctions made of and how many of these form a channel?
connexons (20 types) and 6 subunits associate to form a connexion channel
what governs what can pass through a gap junction?
how big the molecule is and which amino acids line the channel (their polarity etc)
give two examples of a tissue where gap junctions are found
in the heart to allow co-ordinated contraction and in the myometrium to co-ordinate uterine contractions during childbirth
give an example of contact dependent ligand receptor binding
T cell and antigen presenting cell - T cell recognises a pathogen presented on an MHC II
what is the mechanism of contact dependent ligand receptor binding in T cells and APCs?
APC engulfs a pathogen and presents it on MHC II, T cell recognises this and becomes primed, co stimulatory CD80 is upergulated on the APC surface, CD80 simultaneously engages with CD28 on T cell and boosts the signal to allow differentiation of the T cell into the relevant T cell
