4. Receptor -Effector Coupling Mechanism (1) Flashcards
What is receptor superfamily 1?
Receptor operated ion channel
What does superfamily 1 conatain?
Family receptor for neurotransmitter acetylcholine also stimulated selectively by agonist nicotine
competitive reverisible antagonists
competitive irreversible antagonists
What are the subtypes of the nicotinic cholinoceptor?
Several types of some subunits occur
Various homoand heteropentameters formed
Subunit composition and ratio determine physiological and pharmacological properties of receptors
Novel therpeutic applications
What is receptor subfamily type 2?
Indirect linkage to ion channel or enzyme
G-protein coupled receptors
What is the largest superfamily?
Superfamily 2
What are examples of receptors in superfamily 2?
Adrenoceptor family for noradrenaline and adrenaline
Muscarinic acetylcholine receptor family
How many proteins do the receptors in superfamily 2 comprise of?
A single protein
-400+ amino acids in length
What does the receptor in superfamily do?
Weaves in and out 7 times and anchors to cell membrane
What are the 2 families of cholinoceptors?
Nicotinic
Muscarinic
How do the two families of nicotinic and muscarinic cholinoceptors differ?
Nicotine has a low affinity for acetylcholine
Muscarine has a high affinity for acetylcholine
What are the receptors in superfamily 2 also coupled to?
Heterotrimeric G-proteins
What are the features of heterotrimeric G-proteins?
Consists of 3 subunits
Require GTP and GDP for function
Molecular switches
Communicate between superfamily 2 receptor and its effector
What is the basic structure of G protein?
Alpha subunit
Beta subunit
Y subunit
Receptor interaction site
GTP binding site
Effector protein interaction site all on alpha subunit
What is a second messenger?
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
How are second messengers generated within cells?
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
What are the properties of G proteins?
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
What do stimulatory G-proteins do?
Induce conformational change in effector protein to more active state
What do inhibitory G-proteins do?
Induce conformational change in effector protein to less active state
What is the role of G-proteins in health and disease?
Altered expression/RNA stability Mutations- loss/gain of G-protein function implicated in disease Post-translational modifications -phosphorylation -lipid modifications
How do bacterial toxins influence G-protein signalling?
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
How do bacterial toxins influence G-protein signalling?
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
Describe the cyclic AMP signalling pathway?*** check this
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
What processes are regulated by cAMP dependent protein kinase?
Smooth muscle relaxation
Cardiac muscle contraction
Ion transport via voltage-operated channels
Cell growth and differentiation
Cellular metabolism
What are examples of drugs targeting receptors coupled to adenylate cyclase by G-proteins?
B1 adrenoceptors -heart
B2 adrenoceptors (airways)
