W2 - Receptors (Ch 3) Flashcards Preview

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Flashcards in W2 - Receptors (Ch 3) Deck (58):

Describe the types of intracellular communication.

  • contact-dependent: via membrane-bound signal mol.
  • paracrine: mol. released by one type of cell, act on another type
  • synaptic: neurotransmitters released to transmit electrical signals
  • endocrine: hormones released into blood, affect distant cells
  • autocrine: mol. released act on same cell/cells of same type
  • gap junctions: intracell. mol. less than 1200 Da, electrical signals

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Which 4 features characterize a receptor?

  • high affinity to a special ligand (or substrate analogue) ∽ 10-9 mM
  • can be saturated
  • reversible binding
  • evoke a biological response


What is Kd?


defines concentration range in which receptor works best
→ concentration at which 50% of [L] bound to receptor

Kd = [R]*[L] / [RL]

  • [R] = receptor concentration
  • [L] = ligand concentration
  • [RL] = receptor-ligand complex concentration

concept similar to Km (cf. biochem)


What is EC 50?

What is the difference to Kd?

efficient concentration that evokes 50% of the biological response

CAN be = Kd, but doesn't have to (cf. potency, efficacy)


What is the difference btw potency and efficacy?

  • potency: amount of ligand required to produce an effect of given intensity
    → the ↓ [L], the ↑ potency
  • efficacy: ability of ligand-receptor complex to produce a maximum biological response
    → the ↑ response, the ↑ efficacy

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What is the difference btw agonist and antagonist?

  • agonist → biological response
  • antagonist → NO biological response


DO NOT confuse pharmacological/muscular antagonists: 
- pharmacol. ant. inhibit agonist w/o causing an own effect
- muscular ant. cause opposite movement


What is basal activity?

activity of receptor even in the absence of a ligand


Explain different types of agonists and antagonists.

dependent on efficacy

  • full, partial agonists: evokes biological response
  • antagonist (= neutral)
  • inverse agonist: inhibits biological response to a level below basal activity


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Briefly explain the function of a pharmacological agonist in case of diabetes insipidus.

diabetes insipidus = lack of ADH (= vasopressin) 
→ no reabsorption 
⇒ very high V, very low Osm urine excreted (- 20l/d)


⇒ vasopressin-agonist desmopressin administered in form of nasal drops
(would be degraded in intestines if administered per os) 


Why is desmopressin instead of vasopressin administered in case of diabetes insipidus?

  • vasopressin binds to V1 and V2 receptor
  • desmopressin only binds to V2 → no add. vasoconstriction that would incr. blood pressure


What are 2 general classes of receptors?

What are their substrates?

  • plasma membrane receptors: ligands that cannot cross plasma membrane
  • nuclear receptors: small hydrophobic mol. (steroid hormones, thyroid hormones, retinoids, vit D)


What are 2 types of signal transduction pathways of plasma membrane receptors?

intracell. signals = molecular switches 
active - inactive form

  • signaling by phosphorylation: phosphorylation = activation (ATP → ADP + P, P transferred to substrate)
  • signaling by GTP-binding protein: binding of GTP to effector = activation

reverse effects (dephosphorylation, hydrolysis of GTP to GDP) cause inactivation

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What is adaptation?

Other terms.

also: desensitization

reversible reduction (= internalization)/inactivation of receptors due to prolonged exposure to ligand, associated w/ β-arrestin


What are types of plasma membrane receptors?

  • G protein-coupled receptors (GPCRs)
  • ion channel receptors
  • receptors w/ enzyme activity
  • enzyme activity-linked receptors


Explain the structure of G proteins.

  • 7 transmembrane domains
  • heterotrimeric: α, β, γ-complex in resting state
  • in resting state GDP bound to α-subunit


Explain the function of G proteins.

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What are GEFs and GAPs?

  • GEFs: facilitate exchange of GDP to GTP at α-subunit of G protein (activate G proteins)
  • GAPs: enhance hydrolysis of GTP to GDP + P (inactivate G proteins)


List some important G protein families.

  • Gi/0
  • Gq/11
  • G12/13
  • Gs
  • Gt


List effects of the Gi/0 protein family.


  • inhibition of adenyl cyclase
  • activation of K+ channels → hyperpolarization
  • inactivation of Ca2+ channels → no Ca2+ influx
  • phospholipase A2 activation



Explain the cyclic AMP system.

Which family of G proteins stimulate, resp. inhibit it?

  1. a) GS stimulate
    b) Gi/0 inhibit adenyl cyclase
  2. adenyl cyclase: ATP → cAMP (= second messenger)
  3. activates PKA
  4. a) phosphorylates proteins → direct effect
    b) enters nucleus, activates transcription factor CREB → indirect effect

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Which enzyme degrades cAMP?

To ... ?

Example for an inhibitor.

cAMP diphosphoesterase:
cAMP → 5' AMP

caffein = inhibitor

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Which receptors stimulate GS proteins?

β-adrenergic receptors, ACTH receptors (adrenocorticoreceptors)


Which receptors stimulate Gi/0 proteins?

α2-adrenergic receptors, M2, M4 ACh receptors, opiate (μ, δ, κ) receptors 


Where do phospholipase A1, A2, C, and D cleave phospholipids?

  • phospholipase A1: cuts ester bond at C1 
  • phospholipase A2: cuts ester bond at C2
  • phospholipase C: cuts just before phosphate group
  • phospholipase D: cuts just after phosphate group 

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Which G proteins activate phospholipase A2.

Explain its function.

activated by Gi/0

releases arachidonic acid from plasma membrane to be metabolised



List 3 metabolic pathways of arachidonic acid and their products + function.


​COX produce

  • thromboxanes: platet aggregation, vasoconstriction
  • prostaglandins: platelet aggregation, bronchoconstriction, induce inflammation
  • prostacyclins: inhibit platelet aggregation, vasodilation

5-lipoxygenase produces

  • leukotrienes: allergic/inflammatory response (e.g. asthma, rheumatoid arthritis)

epoxygenase produces

  • HETE, EET: incr. Ca2+ release from ER, stimulate cell proliferation

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What are inhibitors of COX 2?


non-steroidal antiinflammatory drugs
e.g. aspirin, ibuprofen



Explain the function of Gt protein transducin.

activates phosphodiesterase in rod cells of the eye in response to light to convert cGMP to GMP 
→ closes cGMP activated cation channels 

⇒ altered membrane voltage

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Which receptors stimulate Gq/11 proteins?

α1-adrenergic receptors, M1, 35 ACh receptors, angiotensin II receptors


Which G proteins activate phospholipase Cβ.

Explain its function.

activated by Gq/11

converts PIP2 → InsP3 (IP3) + DAG

  • InsP3 → binds to ER → opens Ca2+ channels
  • DAG → activates PKC → phosphorylates proteins

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What are ways for Ca2+ to enter the cell other than binding of InsP3 to the ER membrane?

  • via voltage sensitive-Ca2+ channels
  • via other ligand gated-Ca2+ channels


What are store-operated Ca2+ channels?

Relate the concentration of Ca2+ in ECF, cytoplasm and ER.

located in ER membrane, open if Ca2+ content in ER too low 
(in ECF and ER 10-3M, cytoplasm 10-7M)


Explain the role of Ca2+ as second messenger.

Give examples.

  1. binds to calmodulin CaM
  2. activates CaM kinases, e.g.
  • cAMP phosphodiesterase (cf. cAMP degr.)
  • myosin light-chain kinase → sm. mm. contraction

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Which receptors stimulate G12/13 proteins?

What is their function?

thrombin receptors, angiontensin II receptors

⇒ activate Rho


Classify small G proteins.


​also regulated by GAPs, GEFs

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Classify adrenergic receptors according to:

  • subtypes
  • affinity
  • G protein
  • signaling pathway

and name one example.

NE = norepinephrine

E = epinephrine


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Explain the function of ligand gated-ion channel.


signal molecule binds to channel → opens

e.g. acetylcholine binds to nicotinic ACh receptors at neuromuscular junction → Na+/K+ channels open

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What do all excitatory, and all inhibitory ligand gated-ion channels have in common?

List examples.

  • excitatory: ion channels specific to cations
  • inhibitory: ion channels specific to anions

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What are the 2 general types of acetylcholine receptors?

  • nicotinic acetylcholine receptors (nAChRs) = ligand gated-ion channels
  • muscarinic acetylcholine receptors (mAChRs) = G protein-coupled receptors


What types of nicotinic acetylcholine receptors nAChRs are there?

List their specific inhibitors.

  • muscle type: mediates skeletal mm. movement, inhibited by curare
  • neural type: in symp./parasymp. ganglia, inhibited by ganglial blockers


What types of muscarinic acetylcholine receptors mAChRs are there?

List their common inhibitor.

To which G proteins are they coupled?

What is their action?

5 subtypes, M1 - M5 - all inhibited by atropine

  • M1, 3, 5 coupled to Gq/11 → Ca2+, InsP3, PKC
  • M2, 4 coupled to Gi/0 → cAMP ↓, K+ ↑, Ca2+ ↓


What are the 3 types of receptors w/ enzyme actitivity?

Examples for each.

  • receptor guanylyl cyclases: ANP receptor
  • receptor threonine/serine kinases: TGF-β receptor
  • receptor tyrosine kinases: NGF receptor, insulin receptor

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What are the types of receptor guanylyl cyclases?

What is their common function?

  • membrane bound receptor guanylyl cyclases
  • soluble receptor guanylyl cylclases

convert GTP to cGMP


Explain the function of the receptor that binds ANP.

What type of catalytic receptor is it?

GC-Amembrane bound-receptor guanylyl cyclase 

  • structure: ligand receptor, kinase-like domain that binds ATP, catalytic domain
  • ligand = e.g atrial natriuaretic peptide ANP
  • converts GTP to cGMP

 here: inhibited Na+/H20 reabsorption by collecting duct



Explain the function of soluble receptor guanylyl cyclases referring to an example.

  • structure: only catalytic domain w/ α- and β-subunit
  • activated by intracellular NO
  • converts GTP to cGMP

→ here: intracellular ↑Ca2+  binds to CaM → activates NO synthase to produce NO from Arg → activates soluble GC → cGMP relaxes smooth mm.

nitrogylcerin increases NO production → former treatment for angina pectoris

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Explain the function of the TGF-β receptor.

What kind of catalytic receptor is it?

threonine/serine kinase

  • structure: type I, type II subunits, multimeric
  • type I activates downstream effectors

TGF-β binds to type II → phosphorylates type I → activates R-Smad → forms dimer w/ Co-Smad → translocates into nucleus to act. transcription factors

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Explain the general structure of receptor tyrosine kinases w/r/t their function.


  • extracellular domain: cysteine-rich, iG-like, fibronectin type-III-like
  • transmembrane domain: α-helix
  • cytosolic domain: tyrosine kinase, can have tyrosine insert regions (= interrupted) w/ SH2 binding domain

ALWAYS: dimeric → autophosphorylation

different classes: many GF receptors, insulin receptors, etc.

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Name some proteins that can directly bind to the SH2 domain of activated receptor tyrosine kinases.


  • PI 3 kinase → phosphorylates lipids, causes inhibition of apoptosis (cf. own card)
  • GAPs → enhance hydrolysis of GTP, inactivate Ras 
  • PLCγ → same function as PLCβ: PIP2 → IP3 + DAG
  • SOS → Ras-GEF, part of Ras-MAP kinase signaling pathway (cf. own card)

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Explain the function of receptor tyrosine kinases in the Ras-MAP-kinase signaling pathway.

  1. Grb2 recognizes SH2 domain of phosphorylated tyrosine on the activated receptor

  2. recruits SOS by means of two SH3 domains

  3. SOS (= Ras-GEF) stimulates inactive Ras to replace its bound GDP by GTP

  4. activates Ras to relay the signal to MAP kinases (cf. own card)

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Explain the MAP kinase cascade triggered by Ras.

What is the final consequence?

  1. Ras activates MAP kinase kinase kinase Raf
  2. Raf activates MAP kinase kinase Mek
  3. Mek activates MAP kinase Erk
  4. Erk enters nucleus to activate transcription factors

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Explain the pathway of PI 3-kinase activated by receptor tyrosine kinases.

  1. extracellular survival signal activates RTK, recruits + activates PI 3-kinase
  2. PI 3-kinase produces PI(3,4,5)P3 (= docking site for 2 serine/threonine kinases) w/ PH domains
  3. PDK1 and Akt bind to PI(3,4,5)P3 on plasma membrane
  4. phosphorylation + activation of Akt by PDK1 and mTOR → dissociates from plasma membrane
  5. Bad is phosphorylated by Akt → releases apoptosis-inhibitory proteins

⇒ promote cell survival

(phosphorylated Bad binds to a ubiquitous cytosolic protein → keeps Bad out of action)

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What are enzyme activity-linked receptors?


receptors which don't have intrinsic kinase activity, but associate enyzmes

⇒ are dimeric

e.g. receptors for GH, prolaction, cytokines


Explain the function of the GH receptor.


  1. receptor dimerizes in response to GH binding

  2. binds 1+ JAK tyrosine kinases →  phosphorylate themselves and the receptor

  3. STAT tyrosine kinases bind to complex + are phosphorylated

  4. STATs dissociate as dimers + translocated to the nucleus → phosphorylate key transcription factors

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Which proteins can be considered oncogenes?

oncogenes = genes that potentially cause cancer if mutated

  • GF receptors
  • Ras
  • PI 3-kinase
  • Grb2


Explain the function of intracellular receptors.

 hormone either:

  • binds to cytoplasmic receptor that enters nucleus after binding (e.g. cortisol, aldosterone)
  • binds to nuclear receptor that is already in connection w/ DNA (e.g. thyroid hormones, steroids, vit D3, retinoic acid)

⇒ regulate transcription in 2 steps, early/late response

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 What are the 2 ways of signal termination of G proteins?

ligand disassociates, then

  • α-subunit hydrolyses GTP, reassociates w/ βγ-subunit - facilitated by RGS proteins
  • phosphorylation of C terminal by receptor (GPCR) kinase and subsequent binding of β-arrestin
    promotes receptor internalisation
    → G protein cannot access receptor anymore = desensitization


Explain the process of receptor internalisation.

  1. arrestin connects receptor to internalisation protein clathrin
  2. coat assembly of clathrin around receptor
  3. bud formation
  4. vesicle formation, dynamin cleaves connection of receptor to membrane
  5. uncoating, vesicle loses clathrin coat

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Explain the action of insulin upon GLUT 4 receptors.

insulin binding to insulin receptor causes to relocalization of GLUT 4 receptors to plasma membrane to boost glucose uptake

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