Receptor Families Flashcards

1
Q

What is a receptor

What does it do

A
  • A receptor is a bifunctional molecule (principal drug target)
  • It recognises ligands which reversibly bind to a site and the combination of ligand with receptor triggers a response
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2
Q

What are the 4 receptor superfamilies

A
  • Ion channels
  • G-protein-coupled receptors (metabotropic receptors)
  • Kinase-linked receptors
  • Steroid receptors (IC receptors)
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3
Q

What are GPCRs also known as

A

Metabotropic receptors

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4
Q

What are steroid receptors also known as

A

IC receptors

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5
Q

What do VG Ca2+ channels in the heart and BVs influence

A

Heart rhythm and constriction of BVs

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6
Q

In terms of drugs, what are VG Ca2+ channels a target for (2 points)

A
  1. Anti-dysrhythmics (verapamil)
  2. Anti-hypertensives (amlodipine)
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7
Q

What blocks VG Na+ channels

A

Local anaesthetics

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8
Q

What is another name for ligand-gated ion channels

A

Ionotropic receptors

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9
Q

What is a ligand

What happens when a ligand binds to its site on the receptor

Give an example

A
  • A ligand is a small molecule that binds to a receptor
  • It causes conformational change, opening the channel and allowing ions to flow through
  • Nicotinic receptors to which the endogenous ligand ACh binds
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10
Q

How are ligand gated ion channels activated

A

By binding of chemical ligand to a site on the channel molecule

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11
Q

Give an example of a ligand-gated ion channel

Explain how it works

A

Nicotinic ACh receptor

  • Nicotine binds and activates the receptor
  • Allows Na+ and Ca2+ into the cell
  • Stimulant in CNS causes enhanced NT release
  • Also causes release of adrenaline from adrenal gland - fight or flight response
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12
Q

What is nicotine in terms of the ACh receptor

A

A drug that is an exogenous ligand for the ACh receptor

(ACh is the naturally occuring endogenous ligand for this receptor)

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13
Q

Where does the endogenous ligand ACh bind to the nicotinic receptors

What happens as a result

A
  • ACh binds to a site on the alpha subunits opening the channel and allowing Na+ ions to pass through the membrane
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14
Q

Define diazepam

MOA of diazepam

A
  • a benzodiazepine receptor agonist
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15
Q

What is the most abundant class of receptors

What are they also known as

A

G-protein-coupled receptors

Metabotropic receptors

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16
Q

What is the structure of GPCRs/metabotropic receptors

A

7 transmembrane helices (heptahelical), with EC domain usually containing the ligand-binding region

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17
Q

What do GPCRs/MRs possess

A

IC regions that activate G protein signalling molecules (as they bind the guanine nucleotides GTP and GDP)

18
Q

What do GPCRs/MRs do

A

Activate the production of 2nd messengers (cAMP, diacylglycerol/DAG and inositol-1, 4, 5-triphosphate/IP3)

19
Q

Give an example of a GPCR/MR

A

Beta-adrenoceptors: adrenaline/noradrenaline is endogenous ligand (3 subtypes - B1, B2 and B3)

20
Q

What is the effect of activation of GPCRs

A

Phosphorylation of proteins - on/off

21
Q

What happens when beta-adrenoceptors in the heart are activated

A
  • Phosphorylates VG Ca2+ channels
  • Causes the channel to open & Ca2+ comes into the cell
  • Contracts heart muscle
  • Beta blockers prevent this effect
22
Q

What do beta blockers do

A

Prevent activation of beta adrenoceptors in the heart => no phosphorylation of VG Ca2+ channels and Ca2+ does not come into the cell

23
Q

What are G proteins composed of

What does the G protein act as

A

3 subunits - α, β, γ (heterotrimeric)

G protein acts as the interface between the receptor and the enzymes and/or ion channels that are ultimate targets of GPCRs

24
Q

Where is there a binding site for GDP/GTP

What happens when it is occupied by GTP

A

There is a binding site for GDP/GTP on the α subunit

When this is occupied by GTP, the α subunit separates from the other subunits => inactive when GDP is bound

25
Q

G protein coupled receptor structure

A
26
Q

The series of events once the ligand binds to the G protein coupled receptor

A

* G protein has an affinity for GDP when not associated with the receptor

* Effector proteins are embedded in the membrane or IC

  1. Ligand binds
  2. G protein association - exchange of GDP for GTP on a subunit
  3. α subunit dissociates and interacts with effector molecule
  4. Effector molecule activates secondary messengers
  5. Return to resting state following activation of effector molecule
27
Q

Name the endogenous ligands of the GPC B2 receptor

A

Adrenaline & noradrenaline

28
Q

What are kinase-linked receptors also known as

How many membranes do they span

How do they cause an effect within the cell

What are these receptors involved in

Give an example

A
  • Receptors with enzymatic cytosolic domains
  • Single membrane spanning proteins
  • Cause an effect within the cell by adding or removing phosphate groups to or from specific AA residues
  • Many of these receptors are involved in growth and differentiation
  • e.g. insulin receptors (a member of the tyrosine kinases, the largest group)
29
Q

What must tyrosine kinases do in order to produce their effect

A

They must associate & form a dimer

30
Q

Within the action of tyrosine kinases, what happens once a dimer is formed

A

Phosphorylation of tyrosine residues on effector proteins

31
Q

Explain how insulin is an example of a tyrosine kinase

A
  • Promotes uptake of glucose from blood into cells for storage (e.g. as glycogen in liver)
  • Phosphorylates and activates enzymes that synthesise glycogen, and inactivates enzymes that break down glycogen to glucose
32
Q

What are NUCLEAR receptors also known as

A

IC receptors

33
Q

What is the criteria for the ligand of nuclear/IC receptors

A

Must be lipid soluble in order to penetrate the membrane

34
Q

Inactive forms of nuclear/IC receptors that are present in the cytosol or nucleus are associated with…

A

Transcription regulatory factors

35
Q

What happens to nuclear/IC receptors once the ligand binds

What does it affect

Give an example

A
  • Migrate to nucleus when the ligand binds
  • Affects DNA, altering gene transcription and thus translation of RNA into protein
  • e.g. steroid receptors
36
Q

Explain the steps in the MOA of nuclear/IC receptors

A
  1. Ligand enters cell
  2. Ligand binds
  3. Ligand-receptor complex enters nucleus, dimerises and binds to DNA and thus altering cellular protein expression
37
Q

Transcription =

A

DNA makes RNA

38
Q

Translation =

A

RNA makes protein

39
Q

What effect do steroids have on transcription

give an example

what is the response time

A
  • Activate or inhibit transcription
  • e.g. glucocorticoids inhibit transcription of gene for cyclo-oxygenase-2 (COX-2)
  • Anti-inflammatory
  • Slow response because of time to make or destroy proteins
40
Q

Receptor summary

A
41
Q

What are other drug targets besides receptors

A
  • Ion channels
  • Enzymes
  • Transporters