Term
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Definition
| the process by which env. cues (signals) are detected and transduced throughout the cell to elicit a specific cellular response |
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Term
| H2S gas is lethal at about ___ but can be detected about about ___ |
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Definition
lethal at about 300-500 ppm
detected at about -8 ppb |
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Term
| 7 transmembrane receptor is internally what? |
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Definition
| an GEF - a Guanine nucleotide Exchange Factor on a alpha subunit |
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Term
| alpha and Beta-gamma subunits interact with what signaling proteins? |
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Definition
| Effector proteins --> activate downstream events --> gene transcription --> cellular response |
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Term
| G(alpha)s activates what? |
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Definition
| Adenylate cyclase-->converts ATP to cAMP removes inhibition of PKA--> that phosphorylates --> metabolic enzymes (PFK-@), CFTR, CREB (trancription), and heterologous desensitization |
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Term
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Definition
| inhibits adenylate cyclase and hence all the cell responses of AC |
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Term
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Definition
| activates Phospholipase C (Beta-gamma also of alpha(i))--> that cleaves phosphotyl inositol to IP3 and DAG-->IP3 releases Ca+ stores(2nd messn.)-->DAG (along with Ca+)activates PKA. Ca+ also activates PLA2 (inflammation) and binds calmodulin kinase, PKC activates var. substrates |
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Term
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Definition
| activates small G proteins |
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Term
| GPCR signaling, how to get the right G protein mediated response? |
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Definition
different ligands, but same receptor
different lignads bind with different affinities and cell ranges in response |
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Term
| GAP protein (GTPase activator protein) |
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Definition
| increases the rate of ATPase activity, causing the subunits to reform and re-bind the receptor (turn off if ligand isn't off) |
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Term
GAP protein (GTPase activator protein)
or RGS (regulator of G protein signaling) |
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Definition
| increases the rate of ATPase activity, causing the subunits to reform and re-bind the receptor (turn off if ligand isn't off) - Desensitization of the G protein |
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Term
| Heterologous desensitization |
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Definition
Receptor desensitization (heterologous) - PKA and PKC phosphorylate ligand-occupied (active) and unligated GPCRs
Phosphorylated GPCRs can't interact with the heterodimer = cycle broken |
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Term
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Definition
| causes the heterodimer not to be able to bind, it also has an effect on the occupancy of the receptor: lowering the affinity for the ligand |
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Term
| Homologous Desensitization |
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Definition
| free Beta-gamma subunits recruit GPCR kinases (GRKs) that phosphorylate only ligand-occupied GPCRs. These phosphorylated GPCRs recruit and bind Arrestins (Arr)prevents interation with the heterotrimer = no cell response |
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Term
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Definition
| Arr bound receptor is enternalized and degraded or internalized, dephosphorylated, and recycled |
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Term
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Definition
| block binding of NE and EPI inhibiting the fight or flight response. Lowers blood pressure and has a calming effect: decreased HR and CO: useful after a MI by decresing AP and O2 demand |
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Term
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Definition
| targets small intestines & secretes a toxin (ADP-ribosyl transferase) that ribosylates Arg 201 of G alpha s- G alpha s cannot hydrolyze GTP = always active PKC which Phosphorylates CFTR --> salt and water flow into GI = massive diarrhea, dehydration |
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Term
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Definition
| Respiratory system - toxin internalizes (an ADP-ribosyl transferaase) that ribosylates a C-terminal cysteine of G alpha i. modification of this a mino acid blocks binding to AC --> whooping cough |
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Term
| Jenson's metaphysical chondrodysplasia |
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Definition
| mutation in the parathyroid hormone receptor (PTHr) --> ligand-independent G protein activation --> hypercalcemia, increased bone resorption |
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Term
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Definition
| initial opiate dose--> receptor desensitization (need higher dose for same effect)--> required doseexceeds lethal dose = over dose |
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Term
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Definition
non-protein molecules, readily diffusable, amplify a signal
(cAMP, Ca2+, NO, cGMP, DAD, IP3) |
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Term
| downregulation of 2nd messengers |
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Definition
| phosphodiesterarese, channels, metabolic enzymes |
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Term
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Definition
| is activated by cAMP and isa GEF for a small G protein (act like alpha subunit of G proteins) |
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Term
| Luteinizing hormone receptor |
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Definition
| in leydid cells (normal) to activate G alpha s and rise in cAMP --> testosterone production--> puberty |
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Term
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Definition
| luteinizing hormone receptor has an activatin mutation (no ligand) of G alpha s--> premature testosterone production --> spermatogenesis by age 3 yrs old! |
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Term
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Definition
| inactivating mutation of luteinizing hormone receptor --> no G alpha s activation --> no cAMP --> little testosterone production - psuedohermaphroditism |
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Term
| Nitric Oxide Synthase (NOS) |
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Definition
| endothelial cells NOS (regulated by Ca2+) converts Arg and O2 to citrulline, water, and free radical NO. No can diffuse to SMC and activate GC (guanylate cyclase) --> cGMP (2nd messenger)--> vasodilation and SM relaxation |
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Term
| NO (nitric oxide radicals) |
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Definition
in immune cells, such as macrophages, express high levels of diff. NOS isoform in response to cytokines. High amouns of NO toxic to viral and bacterial pathogens
excessive No is toxic to host! |
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Term
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Definition
| cleaves phosphodiester bond of cAMP to generate AMP --> re-inhibition of PKA silencing their act. |
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Term
| Down regulation of DAG and IP3 |
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Definition
| metabolized and recycled by various cellular enzymes |
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Term
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Definition
| calmodulin binds to Ca2+ along with other Ca2+ binding proteins or Ca2+ can be pumped back into storage (SERcA)ATPase |
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Term
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Definition
| iNOS (inducible NO synthase) mRNA is destabilized --> prevents further production of the enzyme and existing iNOS protein is degraded |
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Term
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Definition
| verapamil and nifedipine block Ca+ release --> muscle contractility is inhibited --> dilation of the arteries --> used for angina and hypertension |
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Term
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Definition
bypasses the NOS enzyme and is converted directly to NO--> High levels of cGMP --> vasodilation and SM relaxation
used for treatment of angina or hypertensive emergencies |
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Term
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Definition
| mimics cGMP and competitively interferes with binding of cGMP to PDE (phosphodiesterase) --> no free GMP --> prolonged vasodilation and rise of other things |
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