Strand 3 Flashcards
(45 cards)
What type of responses do cell surface receptors produce? Give examples.
Fast response eg ion channels, G protein coupled receptor and catalytic receptors.
Signalling molecule is hydrophilic and cannot cross the membrane.
What types of response do intracellular nuclear receptors produce? Give examples
Slow response eg regulate gene expression
Signalling molecule is hydrophobic
Which receptors do peptide and steroid hormones attach to ?
Peptide hormones eg insulin - cell surface receptors
Steroid hormone eg testosterone - intracellular (either cytoplasm or nucleus) receptor
The nicotinic receptor is an acetylcholine-gated sodium channel. Is this receptor inotropic or metabotropic and what does it control?
Inotropic - ligand gated ion channel. The receptor is both a receptor and ion channel at the same time.
When Ach binds to muscular nicotinic receptor, ion channel opens and Na+ enters cell, causing depolarisation and Ca2+ to be release from SR. This causes muscle contraction.
What are inotropic receptors?
Ligand gated ion channels. The receptor is both a receptor and ion channel at the same time.
What are metabotropic receptors?
G protein coupled receptors. When a ligand binds to the receptor, a separate ion channel is opened at some point ( they are not the same entity like inotropic)
What is the shortened name for gamma-amino buytyric acid receptor?
GABA A
What type of receptor is GABA A ?
Inotropic inhibitory receptor important in the brain.
What is Gaba A selective for and what activates Gaba A (inhibitory receptor) ?
Cl- ions. It is activated by benzodiazapines, alcohol and anesthetics.
Ach also binds to muscarinic receptors as well as nicotinic receptors. What type of receptor is the muscarinic Ach receptor?
Metabotropic. This receptor is sensitive to muscarine. There are 5 types (M1-M5)
M1,3,5 are stimulatory Gq
M2,4 are inhibitory Gi
What is the difference between GABA A and GABA B?
GABA B is metabotropic and activates a potassium channel, whereas GABA A is inotropic and activates Cl- channel.
Describe the G protein-coupled receptor pathway.
- When a ligand binds to the receptor, GDP (attached to the guanine nucleotide binding site on the alpha subunit) is exchanged with GTP, allowing the alpha subunit to dissociate from the Beta/gamma complex.
- The free alpha subunit activates adenylate cyclase, which produces cAMP.
- cAMP binds to regulatory subunits on PKA, causing the catalytic subunits to dissociate and phosphorylate other proteins.
What are 4 examples of physiological processes mediated by cAMP/PKA pathway?
- Kidney collecting duct - activated by vasopressin and stimulates water retention.
- vascular smooth muscle and cardiac muscle - activated by adrenaline, promotes relaxation of vascular smooth muscle and increases heart rate
- Colonic epithelium - activated by various factors and promotes fluid/ electrolyte secretion.
- Pancreas- activated by glucagon - promotes release of glucose.
What are ways of terminating the signal transduction?
- removing signal
- removing receptor
- removing 2nd messenger
- inactivation of activating signal proteins (GTP hydrolysis and dephosphorylation)
How to remove the 2nd messenger cAMP, and what will this do ?
Phosphodiesterase hydrolyses cAMP, so PKA tetramer is reassembled and signal transduction stops.
What inhibits Phosphodiesterases, and what activates it? (PDE) ?
Inhibited by caffeine
Activated by Ca2+/Cam (calmodium) complex.
How can the beta-adrenoreceptor which binds adrenaline be desensitised to stop the signal transduction?
PKA phosphorylates beta-ARK (adrenoreceptor kinase). Beta-ARK phosphorylates Beta-adrenoreceptor, reducing its affinity to adrenaline, therefore reducing the cellular response.
DAG can mediate desensitisation.
How can proteins be dephosphorylated to stop signal transduction?
protein phosphatases
In GPCR pathway, PKA phosphorylates CREB. What is CREB involved in?
Gene transcription
The alpha subunit in GPCR can be stimulatory or inhibitory. How does cholera toxin affect GPCR?
Cholera toxin acts on alpha s and causes ADP-ribosylation. This prevents GTP hydrolysis which causes persistent activation of alpha subunit, and therefore consistent activation of PKA. This causes CFTR channel to open, so Cl- ions leave epithelial cell, and sodium and water follow to balance the charge - leading to diarrhoea.
What does the pertussis toxin do to GPCR?
Acts on alpha inhibitory subunit and inhibits the inhibitory control of the alpha inhibitory subunit. This means that cAMP and PKA levels increase, as there is no control over it. In airways leads to symptoms of whooping cough.
What two bacterial toxins act GPCR?
- Cholera toxin acts on alpha stimulatory subunit, prevents GTP hydrolysis, therefore constant activation of adenylate cyclase.
- Pertussis toxin acts on alpha inhibitory subunit, stopping the inhibitory effects, therefore cAMP and PKA levels increase.
There are 3 different GPCR. Two (alpha stimulatory and alpha inhibitory) which involve cAMP and PKA. The 3rd type of GPCR is Gq, which involves phospholipase C (PLC). Describe this pathway.
- When a ligand binds to Gq protein, the alpha subunit dissociate and activates phospholipase C cleaves PIP2 into inositol 1,4,5 triphosphate (IP3) and diacylglyerol (DAG).
- IP3 is water soluble and travels through cytosol to ER, causing calcium to be released.
- DAG is hydrophobic and remains in the membrane, recruited protein kinase C (PKC).
What are the two things Ca2+/CaM complex activates?
(calcium calmodium complex involved in Gq GPCR, PLC)
- Actiavtes PDE which degrades cAMP.
- Activates CaM kinases, which are involved in phosphorylation of serine and threonine residues, and also smooth muscle contraction.