deck_662552 Flashcards
Why is signal transduction needed?
Generate a response inside the cell after an effector binds to an extracellular receptor.
What receptor does adrenaline/noradrenaline bind to and what effects does it have?
B-adrenoceptorStimulates adenylyl cyclaseCauses glycogenolysis and lipolysis
What receptors does acetylcholine bind to and what effects does it have?
M3 – Gq proteinStimulates phospholipase CCauses smooth muscle contractionM2 – Gi proteininhibits adeylyl cyclase and stimulate K+ channelsSlows the cardiac pacemaker
What receptors does light have an effect on and what effects does it have?
Rhodopsin receptor – G alpha T transducinStimulates cyclic GMP phosphodiesteraseCauses visual excitation
What does phospholipase C cause?
Causes hydrolysis of PIP2 to generate inositol 1,4,5 - triphosphate and diacylglycerol (InsP3 and DAG)
What G protein does rhodopsin activate and what effects does it have?
Activates G protein called transducinThis activates a phosphodiesterase enzyme which hydrolyses cGMP to 5’GMP
Name two types of drugs which are G protein agonists and the receptors they bind to
B adrenoceptor agonist e.g. Salbutamol/Salmetrol as anti-asthma drugsμ-opioid receptor agonists e.g. Morphine/Fentanyl as analgesia or anaesthetics
Name two type of drugs that are G protein antagonists and the receptors that they bind to
β adrenoceptor antagonists e.g. Propranolol and Atenolol as cardiovascular drugs fro hypertensionD2 dopamine receptor antagonists e.g. Haloperidol and Sulpiride as neuroleptics/ anti-schizophrenic
What is the common basic structure for G proteins?
• Single polypeptide chain (300-1200 amino acids)• 7-transmembrane (7TM)- spanning regions• Extracellular N-terminal • Intracellular C-terminal
What two regions of GPCRs are responsible for receptor binding?
– Is formed by 2/3 of the transmembrane domains– N terminal region or other extracellular domains
Describe the process of signalling by a G protein
- Receptor is activated by binding of substrate2. Activated receptor has a high affinity for GDP-G protein. Binding of this causes GDP to be exchanged for GTP. 3. Alpha-GTPs affinity for receptor and beta/gamma subunit lowers so alpha-GTP and beta/gamma subunit can now interact with effectors. 4. GTPase terminates alpha-GTP reaction, heterotrimer is reformed and awaits reactivation.
How is the length of effector/G-protein interaction determined?
By GTPase activity. This may be regulated by RGS proteins
What can the activated receptor be called in the G-protein activation reaction?
Acts as a guanine exchange factor
How does the cholera toxin interfere with G protein function?
It contains an ADP-ribosyl transferase enzyme which inactivates alpha Gs subunits, leading to irreversible activation by preventing GTPase activity.
What does the interference of the cholera toxin cause?
It causes cAMP production and H2O, K+, Na+, Cl- and HCO3- into the lumen of the small intestine, causes diarrhoea and dehydration
