F6. Receptors and signalling

Question 1

Describe hormones

Answer 1

-Secreted into circulating blood
-Long range communication
-Short and long term effects

Question 2

Describe neurotransmitters

Answer 2

Fast chemical transmission
at neuronal synapses

Question 3

Describe growth factors

Answer 3

Long term control of cell growth
and differentiation

Question 4

Describe paracrine agents

Answer 4

Local control of cell behaviour in the immediate environment

Question 5

common characteristics of receptors?

Answer 5

-selective binding site for native hormone/ transmitter
-act as molecular switches- inactive and active states
-signal is amplified

Question 6

Describe common types of signal amplification

Answer 6

-first messenger e.g hormone binds to receptor
-second messenger: many molecules produced or enzyme activity: many molecules of substrate converted

Question 7

what are the four types of receptors? (from fast to slow)

Answer 7

-ligand gated ion channels
-g protein coupled receptors
-catalytic receptors
-nuclear receptors
ONE NOTE

Question 8

Describe ligand gated ion channels

Answer 8

-fast synaptic transmission (e.g nicotinic receptors)
-acetylcholine binds to acetylcholine receptors causing an influx of Na+ causing depolarisation
-opening a single channel lets 1000s ions flow through

Question 9

Describe G protein coupled receptors

Answer 9

-most common receptor type in the human genome
-amplification: one receptor can activate many G proteins, activated “effector” proteins are often enzymes or ion channels
-three stage system offers variety in messengers recognised and cellular responses generated

Question 10

Describe catalytic receptors

Answer 10

-receptor has enzyme activity activated by hormone binding

Question 11

Describe tyrosine kinase receptors for growth factors e.g EGF mechanism

Answer 11

-Tyr phosphorylation of receptor: a kinase phosphorylates (adds phosphates to) the target protein- common in signalling
-Adaptor proteins: recognise the phosphorylated receptor and produce multiple signals, including gene expression changes
ONE NOTE

Question 12

Describe nuclear receptors

Answer 12

-Ligands diffuse across membranes to intracellular receptors
-active receptors bind DNA and promote transcription
-amplification: many mRNA/ new proteins produced from activated transcription site

Question 13

what do G protein coupled receptors (GPCRs) look like?

Answer 13

-7 transmembrane (7TM) receptors
-Extracellular N terminus
-Intracellular C terminus
-3 extracellular loops (ECL), 3 intracellular loops (ICL)
-Helices are arranged in a bundle
ONE NOTE

Question 14

how many G coupled proteins are there in man?

Answer 14

-around 800 different GPCRs as 7TM “template” allows for many types of binding site

Question 15

what are the different classes of messenger?

Answer 15

-metal ions
-amino acids
-biogenic amines
-lipids
-peptides
-protein hormones
Specific GPRCs for all these different classes of messenger
ONE NOTE

Question 16

what are the 5 main GPCR adrenoceptors for adrenaline/ noradrenaline?

Answer 16

a1-AR, a2-AR, B1-AR, B2-AR, B3-AR

Question 17

Describe receptor subtypes?

Answer 17

multiple receptor subtypes are common for nearly all the messengers you will meet. This is great for pharmacologists to create selective ligands (e.g salbutamol, a B2-AR agonist)

Question 18

Describe adrenoreceptor control of smooth muscle

Answer 18

-The same messenger can affect the same cell type but produce an opposite response. This is due to multiple receptor subtypes coupled to distinct intracellular signalling pathways

Question 19

Describe the flexibility in GPCR signalling

Answer 19

receptor subtypes can activate different G proteins and effectors

Question 20

what are the three main types of G protein?

Answer 20

Gs, Gi, Gq
a particular receptor will normally activate just one type of G protein

Question 21

what G proteins affect what effectors, producing what response?

Answer 21

-Gs, Gi proteins affect Adenylyl cyclase enzyme triggering cAMP
-Gq protein affects phospholipase C (PLC) enzyme triggering intracellular Ca2+

Question 22

how is cAMP formed?

Answer 22

it is synthesised by adenylyl cyclase (membrane enzyme) from ATP
ONE NOTE

Question 23

How does cAMP work as a second messenger?

Answer 23

-cAMP triggers cellular responses by binding and activating protein kiinase A
-PK A then phosphorylates target proteins to change their function
-altered size and charge affects protein conformation/ interactions

Question 24

How does Gs coupled receptors work?

Answer 24

-stimulate adenylyl cyclase e.g B2-AR

Question 25

How do Gi coupled receptors work?

Answer 25

-inhibit adenylyl cyclase e.g a2-AR
-cAMP levels and PK A activity decreased

Question 26

How do Gq coupled receptors work?

Answer 26

-activates membrane enzyme- phospholipase C (PL C)
-PL C hydrolyses a plasma membrane lipid-phosphatidylinositol 4,5-bisphosphate (PIP2)
-Two intracellular messengers are produced: inositol 1,4,5-trisphosphate (IP3) – diffusible
and diacylglycerol (DAG) – membrane bound
-IP3 releases calcium ions (Ca2+) as another 2nd messenger

Question 27

what does DAG produce?

Answer 27

produces signals too (protein kinase C)

Question 28

Increased intracellular Ca2+ results in?

Answer 28

smooth muscle contraction

Question 29

what is the 2nd messenger and function of Gq-coupled receptors?

Answer 29

second messenger: increased IP3, DAG, Intracellular Ca2+
function:
-increased neurotransmitter release, smooth muscle contraction, increased fluid secretion in epithelial cells, increased hormone secretion in endocrine cells

Question 30

What is the 2nd messenger and function of Gs-coupled receptors

Answer 30

2nd messenger: increased cAMP
function:
-increased neurotransmitter release, smooth muscle relaxation, increased fluid secretion in epithelial cells, increased hormone secretion in endocrine cells

Question 31

What is the 2nd messenger and function of Gi coupled receptors?

Answer 31

2nd messenger: decreased cAMP
function:
-decreased neurotransmitter release, smooth muscle contraction, decreased fluid secretion in epithelial cells, decreased hormone secretion in secretory cells