Principle of Cellular physiology 2 Flashcards
Describe the three stages of signal transduction.
- Reception: An extracellular signal molecule activates a membrane receptor which alters intracellular molecules
- Transduction: transduce via a certain pathway
- Response: to activate a cellular response
What is the importance of signal transduction?
It converts one form of signal into a different form
Describe the role of the extracellular signal molecule and the intracellular molecule in signal transduction.
- extracellular signal molecule = first messenger
- intracellular molecule = second messenger system
What is in-between the first and second messenger systems and what is their role in signal transduction?
- Membrane proteins which act as transducers - convert the message of extracellular signals into intracellular messenger molecules that trigger a response
State some of the target proteins and their responses.
- Transport proteins: altered ion transport
- Metabolic enzyme: altered metabolism
- Gene regulatory protein: Altered gene expression
- Cytoskeletal protein: Altered cell shape or movement
- Cell cycle proteins: altered cell growth and division
Give examples of first messengers.
- Amines e.g. epinephrine, adrenaline
- Peptides and proteins e.g. angiotensin 2, insulin
- Steroids e.g. hormones
- other small molecules e.g. amino acids, ions, gases
What are the 4 main classes of receptors?
- Ligand-gated ion channels
- G-protein coupled receptors
- Enzyme-linked receptors
- nuclear receptors
What are the two examples of ionotropic receptors.
- Nicotinic acetylcholine receptor
- GABA receptor
What is an ionotropic receptors?
- They form an ion channel pore
What is a nicotinic acetylcholine receptor?
- A ligand gated ion channel that mediates effects of acetylcholine on muscle
Describe what occurs at a nicotinic acetylcholine receptor.
- Binding of acetylcholine opens a channel and allows Na+ entry
- Binds nicotine
- Electrical event (inward Na+ current) triggers response
- Calcium may also enter from this channel: leads to muscle contraction
What is a GABA receptor?
- A receptor that is an ion channel
- It is selective for Cl- ions
- Naturally activated by GABA - CNS neurotransmitter
- It is an inhibitory receptor
- Has an important role in CNS
- Activated by benzodiazepines
- Activated by alcohol
Give an example of a metabotropic receptor
Muscarinic acetylcholine receptor
What is meant by a metabotropic?
- Indirectly linked with ion channels on the plasma membrane through signal transduction pathways
What activates muscarinic receptors?
Ach
Describe the structure of G-protein coupled receptors.
- Consist of three polypeptide chains: alpha, beta and gamma
- The beta and gamma subunits bind tightly to each other
- The alpha subunit has a guanine nucleotide binding site that binds GTP or GDP
- alpha GDP has a high affinity for beta-gamma
- alpha GTP has low affinity for beta-gamma
- alpha-subunit can hydrolyse GTP
Describe the G protein cycle.
- Unstimulated cell
- Adrenaline binding to beta-adrenoceptor
- Allows beta-adrenoceptor/G protein interaction
- Allows GDP/GTP exchange
- Allows alpha sub unit liberation
- Free alpha sub unit activates Adenyl Cyclase
- Unbinding of adrenaline/GTP hydrolysis
Give three examples of physiological responses mediated by cAMP/PKA
- Kidney collecting duct - activated by vasopressin and stimulates water retention
- Vascular smooth muscle and cardiac muscle - activated by adrenaline and promotes relaxation/increase heart rate
- Liver - activated by glucagon and promotes release of glucose in the blood
Describe the termination of the signal transduction.
- cAMP is hydrolysed by phosphodiesterase (PDE)
- When hormone is removed PDE rapidly clears cAMP from the cell
- Protein reassembles into tetramer and are inactivated
- PDE’s are inhibited by caffeine (explains why heart beats faster after consuming coffee)
What is meant by desensitisation of receptor?
A feedback mechanism to reduce the signal transduction
Describe the mechanism of the desensitisation of receptors.
- Protein phosphorylation leads to cellular response
- PKA phosphorylates beta-adrenoreceptor kinase (beta-ARK)
- beta-ARK phosphorylates beta-adrenoreceptor and reduces affinity for adrenaline
- Reduced affinity leads to reduced cellular response despite sustained stimulation.
