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62 Cards in this Set
- Front
- Back
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What are examples of mediators |
Hormones Cytokines Nucleosides Nucleotides Basic amines Lipids/ fatty acid Enzymes Peptides |
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What is the criteria for mediators |
Released from local cells in sufficient quantity within appropriate time frame Authentic sample of the proposed mediator reproduces the biological effect Interference with the synthesis of mediator modified the original biological response |
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What are eicosanoids |
Group of mediators that are generated from fatty acid precursors |
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Where are eicosanoids not stored |
Not stored preformed in the cell |
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What can eicosanoids mediate |
Mediate paracrine and autocrine signalling |
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What signals do eicosanoids not mediate |
Endocrine signalling |
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Why can eicosanoids not travel far |
Because they degrade quickly so cannot travel far (30s to 5 mins) |
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How do eicosanoids mediate paracrine signalling |
Signal produced which leads to eicosanoid synthesis in cell 1 resulting in the eicosanoids travel to the chosen GPCR causing an effect in cell 2 |
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What is the pathway of autocrine signalling |
A signal is produced and sent to cell 1 where the eicosanoid is synthesised eicosanoid then travels out of the cell and travels to a GPCR on THE SAME cell causing an effect in cell 1 |
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What is the pathway of eicosanoid in endocrine signalling |
Signal is sent to cell 1 where the eicosanoid is synthesised the eicosanoid is then sent outside the cell but fails to travel to cell 2 which leads to the degradation of eicosanoid |
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What enzyme catalysed the EETs in eicosanoids |
Cyt P450 Epoxygenase |
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What are the steps in cell specific roles of prostanoids |
Cell activation leads to local generation of cytosolic phospholipase A2 (cPLA2) CPLA2 integral player in printing AA metabolism Event dependant results in AA esterification and mocked in the cell Depending on the cell that activates depends on the response triggered |
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What happens in endothelial cells when the cox 2 enzymes is present |
Cox2 metabolises AA and promotes synthesis and release of PGI2 This acts in IP receptors on platelets and promotes Gs coupling This pathway protea a rise in cAMP which reduces platelet aggregation If binding of PGI2 to smooth muscle cell IP receptors it results in vasodilation |
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What happens COX1 enzyme catalysed the platelet pathway (shape change) |
COX1 metabolised AA TXA2 is synthesised and upon release will bind to TP receptors on platelets to promote G protein coupling events (Gq, G12/12) This causes platelet shape to change and secretion and ultimately promote increased platelet aggregation |
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What happens COX1 enzyme catalysed the platelet pathway (vasoconstriction) |
After TXA2 is released it binds to TP receptors on smooth muscle cells then Gq couples event promote vasoconstriction |
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What do the events of the cox 1 pathways lead to |
Thrombosis |
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What are NSAIDs |
Non steroidal anti inflammatory drugs |
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What do NSAIDs inhibit |
Prostaglandin and thromboxane synthesis |
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What do NSAIDs do |
Reduce inflammation |
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What effects can NSAIDs have |
Anti thrombotic and analgesic |
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What dk patients lacking cox 1 have |
Mild bleeding disorders |
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What enzyme catalyses the reaction to prostanoids in the eicosanoid AA pathway |
Cox 1 Cox 2 |
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Why are NSAIDs considered non selective |
Inhibit both cox 1-2 |
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What does the inhibition of cox 2 account for |
Anti inflammatory features of NSAIDs |
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What can the inhibition of cox 1 be associated with |
Ulcers Prolonged bleeding Kidney problems |
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Why does Cox 1 inhibition in the GI mucosa lead to peptic ulcers and GI bleeding |
PGE2 which is produced in pathway provides gastric protection in the form of increased mucus secretion, increased bicarbonate and in Seward mucosal blood flow |
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Why does the inhibition of Cox 1 and 2 in the kidney cause Na and water retention, hypertension, hemodynamic acute kidney injury |
PGE2 and PGI2 which are in the cox 1 and 2 pathway in the kidney produces afferent arteriolar vasodilation, increased Na and water secretion |
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Why does the inhibition of cox 1 and 2 do in the cardiovascular system lead to strokes and myocardial infarction |
Cox 1 and 2 promote PGI2 and TXA2 which leads to vascular vasodilation (COX2-PGI2) and platelet aggregation and vasoconstriction is mediated by cox 1 and TXA2 |
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What do PGE1, PGE2 and PGI2 inhibit |
Gastric acid secretion and prevents gastric ulcers |
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What does the lipoxygenase family of enzymes contain |
Iron |
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What are the 3 enzymes involved in the lipoxygenase family |
Leukotrienes LTA4 Hydroxyeicosatetraenoic (5-HETE) Lipoxins |
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What happens when LTA4 hydrolyses leukotriene A4 |
Results in leukotriene B4 formation |
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What enzyme catalyses the reaction to HETEs, leukotrienes and lipoxins in the eicosanoid AA pathway |
LOX |
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What happens when leukotriene C4 synthesises leukotriene A4 |
Leukotriene C4, D4 and E4 are formed |
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How do leukotrienes signal |
GPCRs |
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What are the leukotrienes inflammatory diseases |
Asthma cys Lts Cancer LTB4 |
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What does aspirin promotes the synthesis of |
Anti inflammatory lipoxins |
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What types of tissues can synthesis histamine |
All types |
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When is the rate of histamine increased |
When it is present in inflamed tissues |
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What are the major histamine producing cells |
Mast cells Basophils ECL cells Histaminergic neuron |
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What are the minor producing histamine cells |
Dendritic cells T cells Macrophages Neutrophils Epithelial cells |
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What are triggers for histamine |
Release of mast cells Anaphylatoxins Tissue damage Burns |
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Where is histamine venerated in granules |
Mast cells and WBCs |
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What do cox 1 and 2 enzymes produce |
Prostanoids |
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What does H1 receptor couple with in GPCR |
Gaq |
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What does H2 couple woth in GPCR |
Gas |
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What do H3 and 4 couple to in GPCR |
Gai |
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What happens after histamine binds to H1 receptor |
Influx in Ca2+ Results in smooth muscle contraction Increased capillary permeability Vasodilation Sensory nerve ending pain and itching |
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Whag happens when histamine binds to H2 receptor |
Increase in cAMP production which leads to increased gastric acid secretion Vasodilation in blood vessels Increased capillary permeability |
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What happens when Histamine binds to H3 presynaptic auto receptor |
Decrease in cAMP which results in a decrease in histamine release Decrease in secretion Vasodilation |
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Where is the storage and synthesis or serotonin |
L-tryptophan taken up into cells - converted into 5-HTP - 5-HTP converted into serotonin |
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What are in enzymes involved in serotonin synthesis and storage |
Tryptophan hydroxylase 5-HTP decarboxylase |
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Where is serotonin stored |
Intestine Blood Brain |
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What is the brains physiological function |
Regulation of mood Sleep patterns |
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What does the oxygenation and cyclization of AA produce |
PGG2 and PGH2 intermediates |
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What is physiological role of the blood vessels |
Stored in platelets causes vasoconstriction |
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What is the physiological role of intestine |
5HT mediates motility by activating enteric nee ironed which regulates contraction and relaxation |
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What are examples of prostanoids |
Prostaglandin and thomboxanes |
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What does aspirin irreversibly inhibit |
Cox 1 and 2 |
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What is the cox 1 pathway |
AA is esterified in the membrane phospholipid An inflammatory stimuli promotes phospholipase A2 to form AA Prostaglandins G2 is formed Enzyme Cox1 PG2 into PH2 |
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What is cox 2 pathway |
AA is formed through esterification in the phospholipid which is stimulated by an inflammatory response forming AA AA forms PG2 and PGH2 |
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What are the five different prostanoid receptors |
PGD2 receptors- DP1 and DP2 E2 receptors- EP1-4 F receptor- FP I2 receptor- IP1 and IP2 Thromboxane receptor- TXA2 and TP beta |
