Flashcards in Session 7 Deck (13):
What do cells require in order to respond to extracellular signalling molecules?
What are three types of receptors?
- Ligand-gated ion channel (nicotinic acetylcholine)
- Receptors with intrinsic enzymatic activity (insulin receptors)
- G protein coupled receptors (muscarinic acetylcholine receptors)
What is the function of g protein coupled receptors?
* Muscle contraction
* Stimulus-secretion coupling
* Catabolic and anabolic processes
* Light, taste and smell perception
What is the structure of a g protein coupled receptor?
* Heterotrimeric alpha, beta and gamma subunits
* Beta and gamma bind together and function as a single subunit
How do g protein coupled receptors work?
1. The alpha subunit has a guanine nucleotide binding site which binds GTP and slowly hydrolyses it to GDP
2. Receptor activation leads to GDP being released from the alpha-subunit and GTP binding in its place
3. Binding of GTP decreases the affinity of the alpha subunit for the receptor and the beta-gamma subunit
4. Both the alpha and the beta-gamma subunits are released and can interact with effectors
5. Effector interaction is terminated by the intrinsic GTPase activity of the alpha subunit > GTP hydrolysed to GDP
6. Affinity of the alpha sub-unity for the beta-gamma subunit increases
7. The alpha-beta-gamma subunit is reformed and awaits reactivation by an agonist-activated receptor to re-initiate the cycle
What effect does the pertussis toxin have on g-protein coupled receptors?
* Contains an enzyme which chemically modifies and inactivates Gi type proteins – thus uncoupling the receptor-effector linkage
What effect does the cholera toxin have on g-protein coupled receptors?
* Contains a similar enzyme activity which modifies Gs type proteins
* Leads to irreversible activation – heterotrimeric unit is not reformed
What is adenylyl cyclase?
* An integral plasma protein which can either be activated by Gs or inhibited by Gi via the activation of different receptors
Give an example of a situation in which adenylyl cyclase is activated?
By noradrenaline at beta-adrenoreceptors
Give an example of when adenylyl cyclase receptors are inhibited?
At alpha 2-adrenoreceptors
What does adenylyl cyclase do in cells?
1. The enzyme hydrolyses cellular ATP to generate cAMP
2. cAMP then interacts with protein kinase A
3. PKA then phosphorylates a variety of other proteins within the cells to affect (either positively or negatively) their activities
What does increased cAMP cause in cells?
* Increased glycogenolysis and gluconeogenesis in the liver
* Increased lipolysis in adipose tissue
* Relaxation of a variety of types of smooth muscle
* Postive inotropic and chronotropic effects in the heart