4. Receptor -Effector Coupling Mechanism (1)

Question 1

What is receptor superfamily 1?

Answer 1

Receptor operated ion channel

Question 2

What does superfamily 1 conatain?

Answer 2

Family receptor for neurotransmitter acetylcholine also stimulated selectively by agonist nicotine
competitive reverisible antagonists
competitive irreversible antagonists

Question 3

What are the subtypes of the nicotinic cholinoceptor?

Answer 3

Several types of some subunits occur
Various homoand heteropentameters formed
Subunit composition and ratio determine physiological and pharmacological properties of receptors
Novel therpeutic applications

Question 4

What is receptor subfamily type 2?

Answer 4

Indirect linkage to ion channel or enzyme

G-protein coupled receptors

Question 5

What is the largest superfamily?

Answer 5

Superfamily 2

Question 6

What are examples of receptors in superfamily 2?

Answer 6

Adrenoceptor family for noradrenaline and adrenaline

Muscarinic acetylcholine receptor family

Question 7

How many proteins do the receptors in superfamily 2 comprise of?

Answer 7

A single protein

-400+ amino acids in length

Question 8

What does the receptor in superfamily do?

Answer 8

Weaves in and out 7 times and anchors to cell membrane

Question 9

What are the 2 families of cholinoceptors?

Answer 9

Nicotinic

Muscarinic

Question 10

How do the two families of nicotinic and muscarinic cholinoceptors differ?

Answer 10

Nicotine has a low affinity for acetylcholine

Muscarine has a high affinity for acetylcholine

Question 11

What are the receptors in superfamily 2 also coupled to?

Answer 11

Heterotrimeric G-proteins

Question 12

What are the features of heterotrimeric G-proteins?

Answer 12

Consists of 3 subunits
Require GTP and GDP for function
Molecular switches
Communicate between superfamily 2 receptor and its effector

Question 13

What is the basic structure of G protein?

Answer 13

Alpha subunit
Beta subunit
Y subunit

Receptor interaction site
GTP binding site
Effector protein interaction site all on alpha subunit

Question 14

What is a second messenger?

Answer 14

Intracellular chemical the conc of which can be altered rapidly and reversibly on activation of a cell surface receptor by a chemical mediator to regulate activity of a target present inside cell to produce appropriate

Question 15

How are second messengers generated within cells?

Answer 15

Synthesised inside cell catalysed by enzymes whose activity is regulated by cell surface receptors

Influx of ions via channels whose activity is regulated by cell surface receptors

Question 16

What are the properties of G proteins?

Answer 16

Amplification

• receptor remains active enough long enough to active several G-proteins
• effector remains activated by alpha subunit long enough to generate many molecules of second messenger

Specificity-different alphaG subunits

Question 17

What do stimulatory G-proteins do?

Answer 17

Induce conformational change in effector protein to more active state

Question 18

What do inhibitory G-proteins do?

Answer 18

Induce conformational change in effector protein to less active state

Question 19

What is the role of G-proteins in health and disease?

Answer 19

Altered expression/RNA stability
Mutations- loss/gain of G-protein function implicated in disease
Post-translational modifications 
-phosphorylation
-lipid modifications

Question 20

How do bacterial toxins influence G-protein signalling?

Answer 20

Cholera toxin- Gs family- faulty and switch off

• Arg amino acids impairs GTPase activity
• uncrontrallable increase in activity of Gs/cyclic AMP
• increase in transluminal movement of water/electrolytes can lead to severe diarrhoea

Question 21

How do bacterial toxins influence G-protein signalling?

Answer 21

Cholera toxin- Gs family- faulty and switch off

• Arg amino acids impairs GTPase activity
• uncrontrallable increase in activity of Gs/cyclic AMP
• increase in transluminal movement of water/electrolytes can lead to severe diarrhoea

Question 22

Describe the cyclic AMP signalling pathway?*** check this

Answer 22

Adrenoreceptor will switch on the G protein which in turn acitviates the effector
second messenger activates the cAMP and activates teh protein kinase which unergoes protein phosphorylation and produces a cellular response

Question 23

What processes are regulated by cAMP dependent protein kinase?

Answer 23

Smooth muscle relaxation
Cardiac muscle contraction

Ion transport via voltage-operated channels
Cell growth and differentiation
Cellular metabolism

Question 24

What are examples of drugs targeting receptors coupled to adenylate cyclase by G-proteins?

Answer 24

B1 adrenoceptors -heart

B2 adrenoceptors (airways)

Question 25

What is the cyclic AMP signalling pathway termination of response?

Answer 25

Conformational change due to phosphoprotein phosphate

Dephosphorylation of proteins previously phosphorylated by cyclic AMP-dependent protein kinase

Question 26

What does theophylline do?

Answer 26

Descreases metabolism of cAMP?
relaxes bronchial smooth muscle
some anti-inflammatory effects
stimulates respiratory centre in brain

Question 27

What is theophylline used for?

Answer 27

Therapy for asthma and COPD

rarely uesed now due to side effects