Signalling between Cell II

Question 1

What are the 4 types of signal receiver receptor and how do they work?

Answer 1

1. Ligand-gated ion channel receptors (ionotropic receptors) : ligand binding opens an ion permeable pore.These transmembrane receptors have a central pore incorporated within their quaternary structure.
2. G-protein coupled receptor: ligand binding activates intracellular G-protein
3. Enzyme linked receptor: ligand binding leads to receptor clustering which activates internal enzymes.
4. Intracellular receptor: a membrane permeable ligand binds to a receptor inside the cell.

Question 2

What are IONOTROPIC RECEPTORS and state examples?

Answer 2

1. Ligand binds to receptor protein
2. Configurational change of channel protein
3. Pores open
4. Ions flow through according to concentration gradients

E.g; Receptor, Ligand, Physiological effect

• Nicotinic acetylcholine: acetylcholine, skeletal muscle leading to muscle contraction
• GABAA: GABA, inhibition of neuronal activity
• NMDA, glutamate, synaptic plasticity and memory formation
• 5-HT3, 5-HT, anxiety and emesis.

Question 3

where is it found Nicotinic acetylcholine receptor

Answer 3

On skeletal muscle in neuromuscular junction Can be found in brain as well

Question 4

GABAA

Answer 4

Found on cells in the CNS Opens chloride pores allowing INFLUX If blocked = CNS gets too excited and cause epileptic seizures

Question 5

Describe the activation process of a G-protein coupled receptor

Answer 5

G protein-coupled receptors are also commonly known as 7-transmembrane receptors because the channel protein crosses the cell membrane 7 times.

G protein complex, which consists of an alpha (α) subunit, a beta-gamma (βγ) subunit and an associated GDP molecule.

1. Ligand binds to 7TM receptor, causing confromational changes
2. Heterotrimer binds to 7TMR
3. GDP—> GTP
4. GTP provides energy. G-protein dissociates into 2 active components:
   -Galpha-subunit
   -beta-gamma subunit
   5.Both Gα and Gβγ can act as second messengers
   6.. Alpha and GTP bind to target protein
   7.. ,When the ligand dissociates from the receptor internal GTPase activity on the G-alpha subunit causes the GTP to change to GDP
   GTP—> GDP
   8.. Allows the alpha subunit to unbind and reform the heterotrimer with the GDP attached and GbY subunits.

-Receptor remains active as long as ligand is bound and can activate further heterotrimeric G-proteins.

Question 6

What are two other names for G-protein coupled receptors?

Answer 6

7-TM Receptor

Serpentine Receptor

Question 7

What are the three types of G-protein linked receptor and how do they differ?

Answer 7

Gs Gi and Gq They differ in the alpha subunit

Question 8

Describe the action of Gs-protein linked receptors.

Answer 8

Stimulates adenylate cyclase Adenylate cyclase converts ATP –> cAMP cAMP increases levels of protein kinase A

Question 9

Give an example of a Gs-protein linked receptor and what it causes

Answer 9

Beta-1 adrenergic ,noradrenaline; Ad- adrenaline causes increase in heart rate
D1 dopaminergic: dopamine ligand causes increased neuronal growth

Question 10

Describe the action of Gi-protein linked receptors.

Answer 10

Has the opposite effect to Gs protein linked receptors Inhibits adenylate cyclase, reducing levels of cAMP and PKA. Inhibits PKA

Question 11

Give an example of a Gi-protein linked receptor.

Answer 11

M2 muscarinic, acetylcholine ligand, decreased heart rate
effect: decrease in heart rate
a2 adrenergic..noradrenaline; adrenaline.: vasodilation

Question 12

Describe the action of Gq-protein linked receptors.

Answer 12

• Stimulates Phospholipase C (PLC)
• PLC converts PIP2 to IP3 and DAG
• IP3 stimulates Ca2+ release
• DAG activates Protein Kinase C
  effect: vasoconstriction

Question 13

Give an example of a Gq-protein linked receptor.

Answer 13

AT-1 angiotensin II ligand causes vasoconstriction, increased blood pressure
M3 muscarinic, acetlycholine bronchoconstriction, decreased air flow

Question 14

Describe the action of enzyme-linked receptors.

Answer 14

1. Ligand binding-> receptors clustering
2. Receptors clustering activates enzyme activity within cytoplasmic domain
3. Enzymes phosphorylate receptor
4. Phosphorylation-> binding of signalling proteins to cytoplasmic domain
5. These signalling proteins-> recruit other signalling proteins-> signal is generated within cell
6. The signal is terminated when a phosphatase dephosphorylates the receptor

Question 15

What are the three types of enzymes in enzyme-linked receptor, what is the ligand and effect?

Answer 15

Tyrosine Kinase (95%) , Insulin, glucose uptake nd lipid metabolism
Guanylyl-Cyclase , ANP & BNP, vasodilation, reduction in blood pressure.
Serine/Threonine Kinase, TGF beta, apoptosis.

Question 16

Describe the action of Type 1 Intracellular Receptors

Answer 16

Intracellular receptors are bound to heatshock proteins and are found in the cytoplasm Ligands (usually steroids) pass through the membrane and bind to the receptor Receptor dissociates from heatshock protein The receptor and ligand together move into the nucleus and bind to the DNA and causes increased or decreased transcription These receptors function as homodimers.
Acts as a transcription factor.

Question 17

Describe the action of Type 2 Intracellular Receptors

Answer 17

These are present in the nucleus and are already bound to the DNA The ligand passes through the membrane and through the nuclear envelope and binds to the receptor causing changes in transcription

Question 18

Give an example of a Type 1 Intracellular Receptor. State its ligands, physiological effects and agonists

Answer 18

Glucocorticoid receptor: Cortisol, Physiological effect: Downregulate immune response, increase gluconeogenesis, stress

Question 19

Give an example of a Type 2 Intracellular Receptor. State its ligands, physiological effects and agonists.

Answer 19

Thyroid Hormone Receptor Ligands: Thyroxine, Triiodothyronine Physiological Effect: general physical development, increased metabolism.