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Intergrated Medical Sciences > Pharmacology 1 - Receptors > Flashcards

Pharmacology 1 - Receptors Flashcards

1
Q

What are the 4 types of receptors

A

Type 1- inotropic receptors
Type 2- metabotropic receptors
Type 3- Enzyme linked receptors
Type 4- intracellular signalling and nuclear recpetors.

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2
Q

Define a receptors

A

Transmembrane protein imbedded on the outside of the cell wall which acts as a transducer.

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3
Q

Define type 1 receptors

A

Its inotropic

Associated with fat neurotransmission such as GABA and ACh

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4
Q

How does type 1 receptors work

A

They use nicotinic receptors where two acetylcholine molecules bind to two alpha units allowing the opening of ligand gated sodium channles
= depolarisation

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5
Q

What is intracellular signalling

A

Describes the way a ligand binds to a receptors and activates an enzyme cascade inducing a cellular response.

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6
Q

What are examples of cellular responses

A

Opening if ion channels
Increased secretion of signalling molecules
cell motility

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7
Q

What are the 2 pathways intracellular signalling follows

A

G protein pathway

An enzyme linked cell surface receptor

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8
Q

Define type 2 receptors

A

G couples receptors
Consists of 400-500 residues of a single polypeptide chain.
Forms 7 transmembrane alpha helices arranged with an N terminus and C terminus.

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9
Q

How do ligands bind in type 2 receptors

A

Binds to the binding site of the alpha helices embedded in the membrane.

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10
Q

What units do G proteins consist of

A

3 submits
alpha
beta
gamma

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11
Q

What are the function of each sub unit in G proteins inn type 2 receptors.

A

alpha- functions as GTPase conveying GTP to GDP.

alpha and gamma- form a complex which is hydrophobic and stay closely associated with the membrane.

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12
Q

What are the 3 stages of G protein activation

A
  1. Binding of ligand to the receptors allows a conformational change In shape of the alpha, beta and gamma complex allows the alpha to exchange GDP for a GTPand this causes the alpha to dissociate from the beta and gamma subunits
  2. Alpha coupled to the GTP associates with the allorestic site
  3. Alpha subunit hydrolyses GTP to GDP. This inactivates the enzyme ability of the alpha subunit whilst allowing the activation of the target enzyme
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13
Q

What are 4 of the membrane proteins G proteins use as targets.

A
  1. cAMP
  2. cGMP
  3. Phosplipase C
  4. Ion channels
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14
Q

What is cAMP

A

Secondary messenger

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15
Q

What does cAMP target

A

Inactive protein kinases activating them which is then use ATP as a source of phosphate groups activating them

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16
Q

How is cAMP inactivated

A

by phophodiestererase.

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17
Q

What is phospholipase C

A

based on a membrane bound phospholipid
phosphoionosite
diphosphate PIP2

18
Q

What is the function of PIP2

A

acts as a substrate for a membrane bound enzyme phospholipase C which splits into PIPS into diacylglycerol DAG and insistol 1,4,5 triphosphate

19
Q

What are DAG and Insp3 act as

A

Secondary messenger

20
Q

What does DAG result in

A

in causes protein kinase c activation and InsP3 promotes calcium release form intracellular stores.

21
Q

How does InsP3 allow the promotion of calcium release

A

It binds to endoplasmic receptors and opens endoplasmic calcium channels. This allows calcium to be released in the cytosol where the calcium can interact with a whole range of targets.

22
Q

What cellular activities does InsP3 allow

A

Muscle contraction
Control of secretion from exocrine glands
Hormone release

23
Q

How is cyclic GMP produced

A

Extrafcellualr domain binds the ligand. This causes the intracellular domain to become activated producing cyclic GMP.

This then binds to cyclic GMP- dependent protein kinases which then phosphorylates downstream proteins on either theroinene or serine residues.

24
Q

Define type 3 receptors

A

Transmembrane proteins possessing an extracellular ligand binding domain and a cytoplasmic domain that has intrinsic enzymatic activity.

25
Q

What are the 4 variant types of type 3 receptors.

A
  1. Receptor tyrosine kinases
  2. Receptor linked tyrosine kinases
  3. Receptor tyrosine phosphates
  4. Receptor serine/threonine kinases
26
Q

Describe the role of receptor tyrosine kinases

A

receptors for growth and insulin

Ligand bind to extracellular binding site and induces activation of cytoplasmic tyrosine kinase domains.

Activation of this is achieved via dimesriation so the tit allows cytoplasmic tails croups to phoszphaorylate one another known as autophosphorylation.

They now act as binding sites for a whole mass of proteins contains SH2 AND SH3 domains.

27
Q

What does SH2 and SH3 domains bind to

A

Phosphotyrosine residues to activate receptor tyrosine receptors

28
Q

What components are requires in a signalling process

A
  • Receptors
  • Transdicers
  • Second Messengers
  • Adapter proteins
29
Q

What are adapter proteins

A

consists of mostly SH2 and SH3 domains.
they have no intrinsic function but they couple tyrosine phosphorylated proteins to other proteins that lack SH2 and SH3 domains.

30
Q

What is RAS

A

Is referred as small GTpase

31
Q

What is the function of RAS

A

It functions as a G protein but hydrolyses GTP 100 the slower thus allowing it to remain active for long periods of time

32
Q

What are the 2 regulatory proteins RAS is controlled by

A

GTPase enhanes hydrolyisis rate of RAS

GEFs promotes exchange of GDP to GTP

33
Q

What does the activation of RAS do

A

results in the activation of serine/threonine kinase Raf.

This then causes RAF to phosphorylate MEK this activates serine/theroinine kinase ERK.

34
Q

What dies ERK phosphorylate

A

it phosphosphorylates serine/threonine kinase RAF which allows promotion of transcription of a specific gene.

35
Q

What is an example of receptor linked tyrosine kinases

A

intergrins

36
Q

Define Intergirns

A

Proteins that function mechanically by attaching to the cytoskeleton of the cell wall

37
Q

What does the binding of ligands to an integral cause

A

Allows the beta chain to interact with structural proteins talon and vinculin and adapter proteins

38
Q

What does receptor tyrosine phosphates do

A

Are activated in the same way a receptor tyrosine kinases bu their function is to hydrolyse target proteins so deactivating them.

39
Q

What does the receptor serine/threonine kinases do

A

Again are activated in the same way as receptor tyrosine kinases but they are to specifically phosphorylate proteins.

40
Q

What are type 4 receptors.

A

DNA receptors which are large proteins of 400-1000 amino acids.

Intergrated Medical Sciences (38 decks)

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