Term
| What is the difference between an effector and a second messenger? |
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Definition
effector= enzymes and proteins
molecules= 2nd messengers |
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Term
| Name some of the endogenous ligands that bind GPCRs? |
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Definition
| neurotransmitters (5-HT, dopamine, ACh, glutamate, opioid, norepi, etc.), vasopressin, somatostatin, oxytocin, TSH, postaglandin receptors |
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Term
| Where is the COOH domain? the NH3 domain? |
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Definition
NH3= extracellular
COOH= intracellular |
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Term
| List the three main types of G proteins. |
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Definition
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Term
| Name the different alpha subunit families. |
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Definition
| alpha s, alpha 12, alpha i, alpha q |
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Term
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Definition
PLCB -> PIP2->DAG -> PKC
OR
PIP->IP3 -> Ca2+ |
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Term
| Describe the Gai pathway. |
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Definition
PLA2-> AA
OR AC --> cAMP -> PKA -> CREB |
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Term
| Describe the Gas pathway. |
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Definition
| AC -> cAMP -> PKA -> CREB |
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Term
| Describe the Ga13 pathway. |
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Definition
| Ga13 -> rho/arf -> PKD -> phosphatidylcholine -> choline and phosphatidic acid -> AA |
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Term
| Describe the alpha1 receptor pathway. |
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Definition
| Gq->PLC -> IP3 and DAG from inositol phospholipids. Gq linked receptor store operated calcium channel. Increases intracellular calcium. Aclcium calmodulin stimulates myosin light chan kinase-> contraction |
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Term
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Definition
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Term
| name an alpha 1 antagonist |
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Definition
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Term
| How do alpha 2 receptors work? |
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Definition
| alpha 2 engages Gi and G0 classes of G protein. Gi/0 inhibit adenylate cyclase, reducing cAMP levels; Gi/o increase Ca influx. decrease in cAMP allows calcium-calmodulin stimulation of MLCK activity, causing contraction |
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Term
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Definition
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Term
| What effect on vasculature do presynaptic alpha 2 receptors have? |
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Definition
| indirectly cause vasodilation when NE or EPI binds to the alpha 2 receptor by inhibiting release of NE |
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Term
| What other effects do alpha 2 receptors have other than contraction of vascular smooth muscle? |
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Definition
| indirect effects that lead to vasodilation, aggregation of platelets and decreased insulin secretion |
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Term
| Describe the mechanism of beta receptos? |
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Definition
| activate Gs -> AC -> cAMP (voltage gated Ca channels) -> PKA directly phosphorylates proteins (troponin I) essential for cardiac muscle contraction, stimulates opening of voltage gated Ca channels, inhibits uptake of Ca into cellular stores and cAMP is hydrolyzed by phosphodiesterases |
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Term
| What type of receptor is beta 1? |
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Definition
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Term
| What are the effects of beta 1 activation on the heart? |
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Definition
| positive, ionotropic, chronotropic and dromotropic effects |
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Term
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Definition
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Term
| Name a beta 1 antagonist. |
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Definition
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Term
| What type of G protein is beta 2 receptor? |
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Definition
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Term
| What is the function of an activated beta2 receptor? |
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Definition
| relaxes vascular, bronchial, GI, and GU smooth muscle; stimulates uptake of potassium into skeletal muscle, stimulates glycogenolysis and gluconeogenesis in the liver |
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Term
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Definition
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Term
| Name a beta 2 antagonist. |
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Definition
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Term
| What type of G protein is beta3? |
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Definition
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Term
| What is the function of beta 3 receptors? |
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Definition
| PKA stimulates lipase activity in adipose tissue |
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Term
| What type of receptor is an M1 receptor? |
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Definition
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Term
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Definition
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Term
| Describe the signaling pathway of M2 receptors? |
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Definition
| Gi/o: inhibition of adenylate cyclase and decreased cAMP; activation of K+ channels (e.g. heart), inhibition of Ca2+ channels (e.g. heart) |
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Term
| What effects does M2 receptor activation have on the heart? |
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Definition
| reduced PKA phospohrylation of troponin I and ionic changes cause engative ionotropic and chronotropic effects on the heart |
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Term
| What receptor is M2 the antagonist of? |
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Definition
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Term
| Name an M2 receptor antagonist. |
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Definition
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Term
| Describe the mechanism of an M3 receptor? |
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Definition
| Gq: activation of PLC, production of IP3, and increased intracellular calcium, similar to M1 |
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Term
| What are the physiological effects of M3? |
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Definition
| secretion (bronchial, sweat and salivary, gastric acid). Indirect effect on vasculature: increased synthesis of NO and PGI2 in vascular endothelium causing vasodilation) |
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Term
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Definition
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Term
| Name a non-selective antagonist ofall the muscarinic receptors. |
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Definition
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Term
| What are the different sensitivities for NE vs EPI in the different beta receptors? |
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Definition
| B1 myocardium (EPI=NE), B2 smooth muscle (E, no affinity for NE), B3 adipose (NE>E) |
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Term
| How does beta 1 cause contraction while beta 2 cause relaxation? |
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Definition
PKA phosphorylates contractile machinery proteins e.g. troponin 1 in beta1
PKA phosphorylation of MLCK inhibits myosin function in beta 2 |
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Term
| What is the effect of low versus high epi in vessels in skeletal muscles? |
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Definition
low, beta 2 wins= increased Gs, cAMP = vasodilation
high, alpha 1 wins= increased Gq, Ca2+, overcomes cAMP effects, vasoconstriction |
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Term
| Should you use a low or high dose epi to treat shock? |
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Definition
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Term
| The sum of what two autonomic receptors determines cardiac output? |
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Definition
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Term
| What are possible mechanisms to treat cardiac symptoms of beta blocker overdose? |
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Definition
| glucagon Gs coupled receptor; PDE inhibitor |
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Term
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Definition
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Term
| T/F Arrestin signaling can occur independent of G protein signaling. |
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Definition
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Term
| Antagonists of GPCRs can activate waht molecules? |
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Definition
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Term
| How does carvedilol work? |
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Definition
| beta adrenergic antagonists that acitvates beta 2 arrestin to treat heart failure |
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Term
| Name some examples of TRKs. |
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Definition
| insulin receptor, EGF, VEGF, PDGF, FGF, TNFR |
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Term
| Which receptor can bind to ligands that are proteins attached to other cells for cell-to-cell signaling? |
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Definition
| tyrosine receptor kinases |
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Term
| How do tyrosine receptor kinases transduce a signal? |
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Definition
| ligand binds, receptor dimerizes and phospohrylates itself; phorpohrylated tyrosines provide docking sites for SH2 domains that exist in many signaling molecules |
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Term
| Describe the TRK/RAS pathway. |
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Definition
| TRK, GRB2, SOS, RAS-GDP --> RAS-GTP which phosphorylates RAF, which phosphorylates MED, which phosphorylates ERK |
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Term
| How can Gai/o crosstalk with TRK? |
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Definition
| gamma beta can create Src affecting TRK |
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Term
| What aa is NO produced from? |
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Definition
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Term
| T/F NO can act intra or intercellularly. |
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Definition
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Term
| How does NO cause vasodilation? |
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Definition
| stimulates guanylate cyclase to produce cGMP |
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Term
| How does the endothelial cell know to produce NO to produce vasodilation of the surounding vascular smooth muscle? |
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Definition
| ACh binds to M3 which increases Ca activating eNOS |
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Term
| State the equation by which NO is made. |
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Definition
| L-arginine + O2 + NADPH2---eNOS----> H2O + L-citrulline + NO |
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Term
| Sildenafil works by inhibiting... |
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Definition
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Term
| What is functional selectivity? |
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Definition
| intrinsic property of the drug/receptor interaction whereby different drugs can activate or inactivate one or multiple effector pathways from a single receptor to differentially influence physiology |
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