week 1, Types of receptors

Question 1

How do ligand gated ion channels work ?

Answer 1

When the ligand binds to a ligand gated ion channel it evokes a conformational change opening the channel allowing ions to pass through.

Question 2

What does the direction of ion flow through an ion channel depend on ?

Answer 2

concentration gradient ( ions move high to low) and electrochemical gradient ( +-> - )

Question 3

what is the relative timescale of ligand gated ion channels ?

Answer 3

milliseconds

Question 4

describe Nicotinic ACH receptors

Answer 4

Nonspecific cation receptors
Permeable to Na+, K+ and Ca 2+
Modulate fast synaptic excitation

Question 5

Describe the structure of G-protein coupled receptors

Answer 5

7 trans-membrane domain receptors with G-proteins in proximity.

Question 6

What physiological effect are β2 adrenoreceptors responsible for ?

Answer 6

Broncho dilation

Question 7

Explain the principal transduction pathway of β2 adrenoreceptors

Answer 7

1) Adrenaline binds to the binding pocket on the receptor changing receptors conformation.
2) Gαs binds to receptor promoting the exchange of bound GDP for GTP on the G protein subunit
3) The G-protein activates adenylyl cyclase
4) Adenylyl cyclase converts ATP for cAMP (cAMP is the SECOND MESENGER)
5) cAMP activates PKA
6) PKA inhibits MLCK activity leading to bronchodilation
7) GTP eventually hydrolyses and converts back to GDP and the enzyme is deactivated therefore no more cAMP is made and the reaction is stopped
8) Adrenaline disassociates from the receptor, and it goes back to its original conformation.

Question 8

What physiological effect are α2 adrenoreceptors responsible for

Answer 8

Relaxation of GI tract

Question 9

What is the principal transduction pathway of α2 adrenoreceptors

Answer 9

1) Gαi deactivates adenylyl cyclase
2) Gβγ interacts with K+ channels. K+ leaves the cell and causes relaxation.

Question 10

What physiological response are α1 adrenoreceptors responsible for

Answer 10

vasoconstriction

Question 11

What enzyme is associated with α1 adrenoreceptors

Answer 11

Phospholipase c

Question 12

what is the principal transduction pathway of α1 adrenoreceptors

Answer 12

1) Adrenaline binds to receptor causing conformational change
2) Gαq binds to receptor promoting the exchange of bound GDP for GTP on the G protein subunit
3) Gαq activates phospholipase c enzyme
4) Phospholipase c converts PIP2 into DAG and IP3
5) This causes release of intracellular Ca2+
6) Ca2+ stimulates MLCK activation leading to vasoconstriction

Question 13

what does signal amplification allow cells to do

Answer 13

respond effectively to multiple signals and means fewer receptors are required to evoke a response.

Question 14

Why is Salbutamol used to treat asthma instead of adrenaline

Answer 14

In Pharmacology we want to target a specific response so simply using Adrenaline to treat things like asthma isn’t sufficient due to the wide range of responses it evokes so instead Salbutamol is used as it only targets β2 receptors which causes bronchodilation.

Question 15

What are the main functions of Kinase linked receptors ?

Answer 15

metabolism and growth

Question 16

what is the relative timescale for kinase linked receptors

Answer 16

hours

Question 17

what is an example of a kinase linked receptor

Answer 17

insulin receptor

Question 18

give an overview of the mechanisms of kinase linked receptors

Answer 18

1) Ligands bind to extracellular domain causing phosphorylation of many amino acids within the cell (mainly tyrosine)
2) This initiates a signalling cascade
3) Effecting gene transcription and expression leading to a difference in cell function.

Question 19

Where are nuclear receptors located ?

Answer 19

nucleus

Question 20

What is the relative timescale of nuclear receptors

Answer 20

hours

Question 21

Give an overview of the mechanisms of nuclear receptors

Answer 21

1) Bound by steroid activated hormone – receptor complex forms within the cell
2) Complex binds to DNA and activates specific genes which leads to the production of key proteins

Question 22

what is the structure of nuclear receptors

Answer 22

N terminus -> Activation function site 1 -> DNA binding domain -> hinge -> ligand binding domain-> activation function 2 site -> C terminus

Question 23

What is the physiological effect of β3 adrenoreceptors

Answer 23

thermogenesis

Question 24

What is the backbone of steroid hormones made up of

Answer 24

cholesterol