12. Receptor and Effector Mechanisms

Question 1

What is the effect of ligand binding to ligand-gated ion channels?

Answer 1

It allows ions to move into or out of the cell.

Question 2

What is the effect of ligand binding to receptors with intrinsic enzymatic activity?

Answer 2

Activates an enzyme activity that phosphorylated the receptors and other substrates.

Question 3

What are agonists?

Answer 3

They bind to the receptor and activate it.

Question 4

What are antagonists?

Answer 4

The bind to the receptor but do not activate it, so block the effects of agonists at the receptor.

Question 5

What are examples of B-adrenoceptors agonists and antagonists?

Answer 5

Agonists: B2 specifically, salbutamol and salmeterol (a to-asthma).
Antagonists: propranolol and atenlol (cardiovascular).

Question 6

What are some examples of u-opioid receptor agonists?

Answer 6

Morphine and fentanyl, analgesia/anaesthesia.

Question 7

What are some examples of D2 dopamine receptor antagonists?

Answer 7

Haloperidol and sulpiride, anti-schizophrenics (neuroleptics).

Question 8

What can the results of genetic changes to GPCRs be?

Answer 8

Loss of function or gain of function.

Question 9

What is retinitis pigmentosa caused by?

Answer 9

Loss of function mutation to rhodopsin.

Question 10

What is nephrogenic diabetes insipidus caused by?

Answer 10

Loss of function mutation to V2 vasopressin receptor.

Question 11

What is familial male precocious puberty caused by?

Answer 11

Gain of function mutation to luteinising hormone receptor.

Question 12

What can different GPCRs respond to?

Answer 12

Ions, neurotransmitters, peptide and non-peptide hormones, and large glycoproteins.

Question 13

What is the basic, common structure of GPCRs?

Answer 13

Single polypeptide chain, 7-transmembrane spanning regions, extracellular N-terminal and intracellular C-terminal.

Question 14

Where are the binding site on GPCRs?

Answer 14

Formed by 2-3 transmembrane domains in some receptors of by the N-terminal region in others (if the ligand is large).

Question 15

How do GPCRs cause a change in cellular activity?

Answer 15

Activated GPCR must interact with a G protein. This activates the G protein and causes a change.

Question 16

What is the structure of G proteins?

Answer 16

Made of three subunits: alpha, beta and gamma (although beta and gamma act functionally as one subunit).

Question 17

How are G proteins activated?

Answer 17

By the binding of GPCRs that causes GTP to exchange for GDP on the G protein alpha-subunit.

Question 18

How does a response happen after G protein activation?

Answer 18

The a-By complex dissociates and each then interacts with an effector protein.

Question 19

How is a G protein signal terminated?

Answer 19

The a-GTYP and/or By interaction with effectors lasts until the a-subunit GTPase activity hydrolysed GTP back to GDP. Then a-GDP and By subunits reform the inactive heterotrimaric complex.

Question 20

When acting on B-adrenoceptors, which G protein does the ligand adrenaline/noradrenaline act on? And what is the effect on the effector?

Answer 20

Gsa and it has a positive, stimulatory effect on the effector adenylyl cyclase.

Question 21

When acting on a2-adrenoceptors, which G protein does the ligand adrenaline/noradrenaline act on? And what is the effect on the effector?

Answer 21

Gia, it has a negative, inhibitory effect on the effector adenylyl cyclase.

Question 22

When acting on a1-adrenoceptors, which G protein does the ligand adrenaline/noradrenaline act on? And what is the effect on the effector?

Answer 22

Gqa, has a positive, stimulatory effect on the effector phospholipase C.

Question 23

When acting on rhodopsin, which G protein does the ligand light act on? And what is the effect on the effector?

Answer 23

Gta (transducin) has a positive, stimulatory effect on the effector cyclic GMP phosphodiesterase.

Question 24

When acting on M2/M4-muscarinic receptors, which G protein does the ligand acetylcholine act on? And what is the effect on the effector?

Answer 24

Gia, inhibitory effect on adenylyl cyclase.

Question 25

When acting on M1/M3-muscarinic receptors, which G protein does the ligand acetylcholine act on? And what is the effect on the effector?

Answer 25

Gqa, positive, stimulatory effect on the effector phospholipase C.

Question 26

What do the toxins cholera toxin and pertussis toxin cause?

Answer 26

CTx -> cholera.

PTx -> whooping cough.

Question 27

How does the cholera toxin interfere with G protein function?

Answer 27

It eliminates GTPase activity of Gsa so it is irreversibly activated.

Question 28

How does the pertussis toxin interfere with G protein function?

Answer 28

It interferes with GDP/GTP exchange on Gia so it is irreversibly inactivated.

Question 29

What are the three super families of cell-surface receptors?

Answer 29

Ligand-gated ion channels, receptors with intrinsic enzymatic activity and G protein-coupled receptors.