Lecture 4

Question 1

What is an ionotropic receptor?

Answer 1

A receptor linked to ion channels

Question 2

What is a metabotropic receptor?

Answer 2

A G-protein coupled receptor

Question 3

What is a catalytic receptor?

Answer 3

A receptor linked to kinases

Question 4

What is a nuclear/intracellular receptor?

Answer 4

A receptor linked to gene transcription

Question 5

What is the general structure of an ionotropic receptor?

Answer 5

4-5 transmembrane domains, with one binding domain

Question 6

What is the general structure of a G-protein coupled receptor?

Answer 6

7 Transmembrane domains, often 2 binding sites which can either cytoplasmic or within the membrane, and a G-protein coupling domain which transmits the signal to the G-protein and the structure of which protein is recruited

Question 7

What is the general structure of kinase linked receptors?

Answer 7

1 transmembrane domain, one binding domain and one catalytic domain

Question 8

What is the general structure of a nuclear receptor?

Answer 8

one binding domain and a DNA binding domain, NO transmembrane domain

Question 9

What are examples of ionotropic receptors?

Answer 9

nicotenic acetylcholine receptors (nACh) and GABAa

Question 10

How fast are ionotropic receptors?

Answer 10

Very fast act within ms as the signal is very simple

Question 11

What is the mechanism of ionotropic receptors?

Answer 11

Binding of the agonist causes a conformational change in the receptor which leads to ion channel opening

Question 12

What effects can different agonists have on ionotropic receptors?

Answer 12

Some such as nAChR can cause increased channel opening time, while others such as glutamate can cause an increase in channel conductance
Others can alter the charges lining the pore to alter the selectivity of the ion channel

Question 13

What is the structure of the nACh receptor?

Answer 13

Pentamer of two alpha units, one gamma unit, one beta and one sigma unit, with two ACh binding sites between the alpha and gamma subunits

Question 14

What drugs affect the GABAa receptor?

Answer 14

GABA opens the pore to allow Cl- flow inhibiting neuronal firing, benzodiazepines and barbiturates facilitate the opening of the channel by increasing either the rate r duration of channel opening

Question 15

How fast are G-Protein linked receptors?

Answer 15

fast actions occur within seconds

Question 16

What are examples of G Protein linked receptors?

Answer 16

mAchR, adrenoreceptors

Question 17

What is the mechanism of G-protein linked receptors?

Answer 17

Binding of the agonist binds to the G protein causing a conformational change, this results in the G protein having GDP replaced by GTP which allows signalling to target proteins to cause the desired biological effect, the GTP will eventually be hydrolysed leading to the end of the signal

Question 18

What are the G protein families?

Answer 18

Gs (stimulatory), Gi (inhibitory), Gq

Question 19

What is an example of a target protein of a G-protein linked receptor and what is its function?

Answer 19

Adenylate kinase can be activated, this can generate cAMP as a secondary messenger which will activate various protein kinases
If Gi is activated then there will be a decrease in cAMP if Gs is activated there will be an increase in cAMP

Question 20

What is the role of protein kinases?

Answer 20

Enzymes that attach phosphate groups to proteins (like PKA, PKC) leading to changes in structure and function, this can sometimes operate on 3rd messengers to cause regulations of genes

Question 21

What is bi-directional control with regards to G-proteins?

Answer 21

Different G-receptor complexes allow opposing effects on an enzyme allowing for a graded signal and a maintenance of balance

Question 22

What is the function of Gq?

Answer 22

Gq activates phospholipase C which activates IP3 which can open Ca2+ channels on the ER or SR, this can activate protein kinase C which will result in the phosphorylation of substrates
this pathway is key to smooth muscle contractions

Question 23

How fast are catalytic receptors?

Answer 23

Can act between minutes or days, dependent on the pathways involved

Question 24

What are examples of catalytic receptors?

Answer 24

Tyrosine kinase and guanylate cyclase receptors which respond to ligands such as growth factors, hormones and cytokines to trigger a kinase cascade

Question 25

What is the Ras/Raf/MAP Kinase pathway?

Answer 25

A pathway involved in cell differentiation, Growth factor binds onto a receptor causing dimerisation and autophosphorylation of tyrosine residues on the intracellular tyrosine kinase domains, this results in the binding of an SH-2 domain protein which becomes phosphorylated and signals Ras to become activated, this activates Raf, which results in a phosphorylation chain moving from Raf to Mek to Map kinase which phosphorylates various transcription factors altering gene transcription

Question 26

What is the Jak/Stat pathway?

Answer 26

Cytokine binds to a receptor which is a dimer, when both of the dimers are bound a conformational change is induced resulting in Jak being recruited and phosphorylating tyrosine residues Stat then binds and becomes phosphorylated leading to it to dimerise and alter gene transcription

Question 27

How fast are intracellular receptors?

Answer 27

Slow acting often taking hours or days to take effect but have a long lasting effect

Question 28

What are examples of of intracellular receptors?

Answer 28

Steroid hormone receptors

Question 29

What is important about the ligands of intracellular receptors?

Answer 29

need to be able to easily penetrate the cell membrane and therefore are frequently lipid soluble

Question 30

What is the mechanism of intracellular receptors?

Answer 30

Typically there is an inhibitor bound to the ligand binding domain this will be removed by the hormone which will allow the receptors DNA binding domain to bind to highly conserved regions of DNA to alter gene transcription and protein synthesis