Receptor Transduction Systems 2 Flashcards Preview

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Flashcards in Receptor Transduction Systems 2 Deck (34):
1

what do GPCRs systems found in the cell membrane consist of?

- GPCR receptor protein itself
- G-protein (heterotrimeric, alpha-beta-gamma), alpha subunit binds GTP when active, hydrolyses to GDP to turn off signalling
- effector proteins including: enzymes, ion channels

2

why do we need GPCRs?

they allow conserved signalling machinery to generate incredibly complex responses

3

what types of responses do GPCRs allow?

1. amplification
2. diversity

4

what does amplification consist of?

- one receptor may activate multiple G proteins
- one g-protein may activate multiple effector enzymes

5

what does diversity consist of?

- a single receptor may activate different classes of G-protein with unique signalling properties
- one G-protein may activate different types of effector
- G-protein heterotrimer components: alpha and beta-gamma subunits may activate different effectors

6

how are heterotrimeric G-proteins grouped?

they are grouped into 3 primary classes based on their downstream signalling properties

7

which are the types of heterotrimeric G-proteins?

1. Gs family: activates cyclase to increase cAMP
2. Gi family: inhibits adenylate cyclase to decrease cAMP
3. Gq family: activates phospholipase C to produce IP3 and DAG

8

what do beta-adrenoceptors do?

they activate adenylate cyclase: ATP--> cyclic AMP (cAMP)

9

what are the effects of increased cAMP?

1. heart (beta1): increase heart rate and force of heart beat
2. lungs (beta2): relaxes bronchial smooth muscle

10

what are the effects of agonists in the lung?

- dilates bronchial smooth muscle
- eases respiration
- used in asthma

11

what are antagonists in the heart?

- competitive reversible antagonist
- slows heart rate and reduces force of beat
- used in cardiovascular disease e.g. hypertension

12

what activates alpha1-adrenoceptor?

Epinephrine

13

where is alpha-adrenoceptor expressed?

In smooth muscle

14

why does alpha-adrenoceptor couples to Gq protein?

because it activates PLC to generate IP3 and DAG

15

how does alpha-adrenoceptor increases intracellular Ca2+ concentration?

by:
- release from SR (IP3)
- through membrane channels (DAG)

16

what does Ca2+ do?

stimulates smooth muscle contraction

17

what is prazosin?

a competitive reversible antagonist of the alpha1-adrenoceptor

18

what does prazosin do?

prevents contraction of smooth muscle in blood vessel wall

19

how does prazosin work?

it dilates blood vessels so blood pressure falls

20

what is prazosin used for?

to treat cardiovascular disease e.g. hypertension

21

other cell responses regulated by Gq Inositol-Phospholipid signalling

1. liver - vasopressin - glycogen breakdown
2. pancreas - acetylcholine - amylase secretion
3. smooth muscle - acetylcholine - contraction
4. blood platelets - thrombin - aggregation

22

what is a tyrosine kinase?

an enzyme that can transfer a phosphate group to a tyrosine residue in a protein

23

where is phosphorylation important?

in signal transduction to regulate enzyme activity

24

what do tyrosine kinase receptors link?

an extracellular ligand binding domain with an intracellular tyrosine kinase domain

25

what is dimerisation?

coupling by an agonist binding to 2 receptors

26

what is a receptor tyrosine kinases (RTKs)?

a cell membrane receptors containing a single TM domain

27

what activates RTKs?

hormones and growth factors e.g. insulin, AGF

28

what happens when RTKs activate?

upon receptor activation, they form a dimer and autophosphorylate

29

what happens after the formation of a dimer and autophosphorylation?

a kinase cascade is activates that ultimately phosphorylates a transcription factor

30

what do RTKs do?

regulate gene expression, growth, metabolism

31

examples of drugs that inhibit RTK signalling

1. Imatinib (Gleevec)
2. Lapatinib (tykerb)
3. Trastuzumab

32

what is imatinib?

a small molecule tyrosine kinase inhibitor for chronic myelocytic leukemia

33

what is lapatinib?

a small molecule EGF receptor inhibitor approved in US for breast cancer

34

what is trastuzumab?

a monoclonal antibody against EGF used primarily again in breast cancer