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Organisation of the Body

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show High affinity for hormone Hormone specific Binding is saturatable  
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show Binding constant 10^-12 to 10^-9 Very little hormone needed for activation  
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EC50   show
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show Ligand gated ion channels G protein coupled receptors Enzyme linked Intracellular receptors  
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Ligand gated ion channels   show
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nACRs   show
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show 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  
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G protein coupled receptors   show
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What activates GPCRs   show
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show Around 820 in the human body All have similar structures - hard to design drugs specific to one, so unwanted effects are common  
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show 7 transmembrane regions Extracellular N-terminus Often post translationally glycosylated and phosphorylated to regulate activity  
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M2 muscarinic receptors   show
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show 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  
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show Gq - activates PLC Gi - inhibits adenylate cyclase Gs - stimulates adenylate cyclase G12/13 - Rho family Gb - activates inwardly rectifying potassium channels  
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The G protein cycle   show
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Downstream effectors of GPCRs   show
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Adenylate cyclase   show
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Effects of Cholera   show
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show ACTH stimulates Gs - cAMP produced Immediately upregulated cholesterol synthesis by cholesterol ester hydrolase Over a few hours allows uptake of cholesterol by mitochondria  
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show 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  
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show 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  
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show Channels phosphorylated - less active e.g. G protein gated inwardly rectifying potassium channels in the heart  
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show Uses multiple mechanisms Ligand gated ion channels Voltage gated ion channels Gq proteins - IP3 activates Ryr channels  
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show Reaction cascades cause massive signal amplification Proteins made can last a long time, so short activation affects function for longer periods  
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Enzyme linked channels   show
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show 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  
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Intracellular receptors   show
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show DNA strand contains specific hormone response elements Contains regions for transcriptional regulation, DNA binding and hormone binding  
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What binds to intracellular receptors   show
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Turning off the signal   show
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Desensitisation of GPCRs   show
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show Phosphatases remove the phosphate from the C terminus Causes arrestin to dissociate  
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show Serves as a connection between glucagon and insulin pathways Insulin drives activation of phosphodiesterase to downregulate the role of glucagon Breaks down cAMP  
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show 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  
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show Failure of ligand binding Failure of signal transduction Constitutively active signal receptor systems Antibodies to receptor  
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Inactivating receptor mutations   show
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show Receptor continually active without hormone bound  
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show 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  
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Activating receptor mutations   show
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Physiological response to receptor activation   show
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Types of cell signalling   show
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