Help
Options
Question
Characteristics of hormone receptors
click to flip
Didn't know it?
click below
click below
Knew it?
click below
click below
Don't know
Question
Kds
Remaining cards (40)
Know
retry
shuffle
restart
0:00
Embed Code - If you would like this activity on your web page, copy the script below and paste it into your web page.
Normal Size Small Size show me how
Normal Size Small Size show me how
Cell Signalling
Organisation of the Body
| Question | Answer |
|---|---|
| Characteristics of hormone receptors | High affinity for hormone Hormone specific Binding is saturatable |
| Kds | Binding constant 10^-12 to 10^-9 Very little hormone needed for activation |
| EC50 | Conc of hormone that gives 50% response |
| Receptor classes | Ligand gated ion channels G protein coupled receptors Enzyme linked Intracellular receptors |
| Ligand gated ion channels | Open in response to NTs Leads to a change in membrane potential due to ion movement Instantaneous response |
| nACRs | 5 protein 2 homodimers and 1 extra protein Blocked by cobra toxins Open in response to ACh binding - non-selective cation channel |
| Katp channel | Glucose enters beta cells and is metabolised to produce ATP This binds to K channels and blocks them Leads to depolarisation and Ca influx Insulin release triggered ATP acts as a hormone |
| G protein coupled receptors | Hormone binds to receptor leading to G protein mobilisation They interact with enzymes through a second messenger system Timescale - seconds/minutes |
| What activates GPCRs | Protein hormones - glucagon Amines - adrenaline Lipids - prostaglandins |
| Family of GPCRs | Around 820 in the human body All have similar structures - hard to design drugs specific to one, so unwanted effects are common |
| Structure of GPCRs | 7 transmembrane regions Extracellular N-terminus Often post translationally glycosylated and phosphorylated to regulate activity |
| M2 muscarinic receptors | Found in the heart - slow heart rate QNB - antagonist |
| G proteins | Get their name from their ability to bind GTP and GDP They exist in an active GTP bound and an inactive GDP bound form Active G proteins bind and activate signalling enzymes causing a specific response Heterotrimeric - alpha, beta and gamma subunits |
| Types of GPCRs | Gq - activates PLC Gi - inhibits adenylate cyclase Gs - stimulates adenylate cyclase G12/13 - Rho family Gb - activates inwardly rectifying potassium channels |
| The G protein cycle | Inactive - loosly associated with proteins Ligand binds and recruits G proteins GTP exchange causes dissociation of the protein Subunits have different effects GTP hydrolysis causes reassociation |
| Downstream effectors of GPCRs | Adenylate cyclase Phospholipase C Ion channels |
| Adenylate cyclase | Stimulated by Gs and inhibited by Gi Converts ATP into cAMP This activates PKA by releasing its catalytic subunits cAMP degraded by phosphodiesterase |
| Effects of Cholera | A GPCR agonist Binds to Gs - increased cAMP and PKA Activates CTFR Overactive CTFR causes Cl loss into lumen of gut followed by Na and water Leads to internal dehydration Enkephalin - stimulates Gi to reduce effects |
| cAMP in steroid synthesis | ACTH stimulates Gs - cAMP produced Immediately upregulated cholesterol synthesis by cholesterol ester hydrolase Over a few hours allows uptake of cholesterol by mitochondria |
| PLC | Activated by Gq receptors Cleaves PIP2 into DAG and IP3 DAG activates PKC - phosphorylates proteins IP3 activates store operated calcium ion channels leading to Ca efflux from SR - activation of intracellular proteins |
| Role of Gq/Gs switch in beta cells | Normal B cells us a Gs pathway to secrete insulin involving GIP and GLP-1 Following chronic hyperglycemia and chronic sulfonylurea treatment they switch to Gq |
| Ion channels in GPCR | Channels phosphorylated - less active e.g. G protein gated inwardly rectifying potassium channels in the heart |
| Smooth muscle contraction | Uses multiple mechanisms Ligand gated ion channels Voltage gated ion channels Gq proteins - IP3 activates Ryr channels |
| Amplification | Reaction cascades cause massive signal amplification Proteins made can last a long time, so short activation affects function for longer periods |
| Enzyme linked channels | Receptor is also the effector enzyme e.g. tyrosine cyclase enzyme activity Receptors dimerise on ligand binding Autophosphorylation at tyrosine and serine residues |
| Insulin receptor | Tyrosine kinase receptor Leads to insertion of Glut4 into cell membranes Under fasting conditions no insulin = no glucose uptake as no Glut4 channels in membrane |
| Intracellular receptors | Control of DNA transcription e.g. steroid hormones and Vit D (for Ca uptake) Takes hours for proteins to be produced |
| Steroid receptor structure | DNA strand contains specific hormone response elements Contains regions for transcriptional regulation, DNA binding and hormone binding |
| What binds to intracellular receptors | Androgens Estrogen Progesterone Glucocorticoids Mineralocorticoids Thyroid hormone Vit D |
| Turning off the signal | Removal or degradation of the hormone Desensitisation of the receptor Internalisation of the receptor |
| Desensitisation of GPCRs | Phosphorylation of certain residues at the C terminus by GRK Arrestin binds to the receptor and prevents G protein interaction |
| Resensitisation | Phosphatases remove the phosphate from the C terminus Causes arrestin to dissociate |
| Role of phosphodiesterase's in glucose control | Serves as a connection between glucagon and insulin pathways Insulin drives activation of phosphodiesterase to downregulate the role of glucagon Breaks down cAMP |
| Receptor internalisation | Receptors taken into the cell by endocytosis Basically receptor mediated endocytosis Dopamine D1 receptors are permanently downregulated due to overuse in addiction - via internalisation and DNA metylation |
| What causes disease at receptors | Failure of ligand binding Failure of signal transduction Constitutively active signal receptor systems Antibodies to receptor |
| Inactivating receptor mutations | Receptor does not function despite hormone present |
| Activating receptor mutations | Receptor continually active without hormone bound |
| Dwarfism | Due to growth hormone releasing hormone inactivating receptor mutations No signalling - reduced growth hormone release No long bone or muscle growth Treated by administering growth hormone |
| Activating receptor mutations | Precocious puberty - puberty starting at 5-9 years Constant activation of LH receptors without the presence of the hormone Ovary - estrogen Testes - testosterone |
| Physiological response to receptor activation | Vesicle fusion Gene transcription Protein production |
| Types of cell signalling | Depolarisation induced - Ca entry dependant Depolarisation independent - Ca entry dependant |
Created by:
12345678987654321000000
Popular Medical sets