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55 Cards in this Set
- Front
- Back
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what are autocoids |
substances that produce an effect in tissues in which they are releasedwhat |
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what do autocoids act on |
act on cells which release them (autocrine) act on cells in close vicinity (paracrine) |
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examples of autacoids |
bradykinin histamjne 5-HT- serotonin |
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what is bradykinin |
inflammatory mediator. it is a peptide that causes blood vessels to dilate 9 amino acid peptide chain |
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kininogens are the precursors to what |
kinins |
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what are kinins formed by |
cleavage of kinogens by the enzyme kallikerin. |
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kallidin (KD) is often referred to as what |
as lys- bradykinin is a decapeptide can be converted to BK BY aminopeptidase enzymes |
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what are the bradykinin receptors |
B1 and B2 B3-B5 less known |
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what is the rank order potency of kinins at B1 receptor |
des-arg9 BK> lysBK>>BK preferentially activated by kinins lacking the C-term arg residue |
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rank order potency of kinins at the B2 receptor |
Lys-BK>>> des-arg9 BK HIGH affinity for BK and Lys-BK(kallidin) |
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where does a lot of sucessful medication come from |
using GPCR as a target looking at the way they work for therapeutic value |
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what are bradykinin agonists |
peptide ligands B1: R-838 (modifyed to create side chains so better specificity) B2: labradimil |
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bradykinin antagonists |
substituted peptides B1- leu-des-arg BK OR Lys-leu- des -arg BK B2- D-arg-BK |
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antagonist of bradykinin is by doing what |
modifying amino acids in the 9 amino acid sequence |
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what is a peptidominetic ligand for bradykinin |
b2= firazyr for hereditary angiodemia (HEA) |
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typical signalling cascades Of BK/kinins |
releases of intracellular Ca2+ activates PLA2 release of PGI2 and/or NO |
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what happens when kinins bind to B2 receptors |
kinin binds to B2 promotes Gq coupling pathway which triggers a rise in intracellular calcium levels that promotes PLA2 dependent release of arachidonic acid and prostacyclin synthesis |
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what is the full pathway of kinin binding( coupling mechanism) |
kinin bind to B2 receptor, Gi coupling pathway, stimulates phospholipase C, calcium mobslisation, phospholipase A2 and then esterification of arachidonic acid |
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what are other outcomes in actions of BK/kinins |
vascular leakage pain contraction/relaxation of smooth muscle transport of water and ions |
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explain BK AND inflammation |
inflammation causes extravasation and activayion of kininogenases (kallikerins) produces more bradykinin increase kallikerins increase bradykinis release of inflammatory PG mediators |
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what happens during inflammation with BK |
up-regulation of b1 receptor(upregulated receptor- more opportunity to bind) release of B1 receptor agonists -vasodilation -odemea -increased vascular leakage |
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physiological and pathophysiological roles for BK - vasodilation |
anti hypertensive septic shock pancreatitis |
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physiological and pathophysiological roles for BK increase in vascular permeability |
pancreatitis hepatorenal syndrome edema rhinitis |
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physiological and pathophysiological roles for BK release of inflammatory mediators |
rhinitis asthma colitis arthritis |
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physiological and pathophysiological roles for BK stimulation of sensory nerves |
pain arthritis |
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physiological and pathophysiological roles for BK contact activation |
Alzheimer’s disease |
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physiological and pathophysiological roles for BK GLUT 4 translocation |
improvement in insulin sensitivity |
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physiological and pathophysiological roles for BK ischemic preconditioning |
prevention of infarction remodelling arehythmias |
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physiological and pathophysiological roles for BK release of NO, PGI2 and t-PA |
anti hypertrophic proliferative aggregationally atherosclerotic |
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histamine formed by |
decarboxylation of L-histidine, by histidine decarboxylase |
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what are histamine synthesis and inactivation |
all tissues can synthesise histamine rate of synthesis increased in inflamed tissues metabolised by histamine N-methyltransferase (HNMT)and diamine oxidase (DAO) to give methyl imidazole acetic acid |
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explain histamine release and what its triggered by |
generated in granules of mast cells and WBCs histamine release is triggered by allergens binding to mast-cell-bound IgE antibodies causing degranulation |
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other triggers of histamine release |
release from mast cells via sensory pain receptors anaphylatocins tissue damage, heat mechanical injury |
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histamine is release by what |
exocytosis that can lead to inflammation and further cellular damage |
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what are histamine receptors |
GPCRs- H1-H4 |
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what are histamine receptors |
GPCRs- H1-H4 |
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what do histamine receptors couple to |
H1 couple to Gaq H2 couple to Gas H3 and H4 couple to Gai |
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what happens when histamine binds to H1 receptors |
increased ca2+ leads to smooth muscle contraction increased capillary permeability vasodilation |
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what happens when histamine binds to H2 receptors |
increased cAMP Leads to increased gastric acid secretion- blood vessels: vasodilation increased capillary permeability |
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what happens when histamine binds to H3 receptors |
decrease in cAMP leads to decrease in histamine release decrease in secretion and vasodilation |
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give an example of a H1 antagonist and their functions |
mepyramine, promethazine used for allergic conditions- skin reactions and hay fever |
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give and example of H2 antagonist and their functions |
Ranitidine/cimetidine treatment of peptic ulcers/stomach acid production
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what is cinetidine |
selective H2 antagonist for gastric ulcers |
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what is 5-HT |
it is a monoamine neurotransmittee |
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how do you get synthesis of 5-HT |
L-tryptophan is taken up into cell converted into 5-HTP 5-HTP is then converted into 5-HT |
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enzymes involved with the synthesis of 5-HT |
tryptophan hydroxylase 5-HTP decarboxylase |
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where are 5-HT Stored and when they are released |
intestine- enterochromaffin cells- released during stimulation of gut blood- platelets-released during clotting brain- neurones- released during nerve stimulation |
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what does 5-HT DO to the intestine |
mediates motility by activating enteric neurones which regulates contraction and relaxation |
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what does 5-HT DO to the intestine |
mediates motility by activating enteric neurones which regulates contraction and relaxation |
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what does 5-HT DO in platelets |
causes aggregation, also causes vasoconstriction (prevents blood loss) |
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what does 5-HT DO to the intestine |
mediates motility by activating enteric neurones which regulates contraction and relaxation |
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what does 5-HT DO in platelets |
causes aggregation, also causes vasoconstriction (prevents blood loss) |
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what does 5-HT DO to the brain |
regulation of mood, sleep patterns |
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whats an example of a selectin serotonin reuptake inhibitor and function |
fluxoeine inhibits serotonin reuptake via sert higher levels of 5-HT In the synaptic cleft to activate the receptor |
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why is mediator biology an extensive subject |
insight into functions of molecules released in body that produces pharmacological effects mediators that trigger disease and subsequently exploit for developing new therapies |
