Receptors 1 Flashcards
What are the two types of intercellular signalling?
- Signalling by secreted molecules
2. Signalling by plasma membrane- bound molecules
What are the 3 types of Signalling by secreted molecules?
- Paracrine
- Endocrine
- Synaptic
Describe paracrine signalling
•If a signalling molecule is secreted into a tissue and acts on adjacent cells - signalling molecule is called a local mediator
When is it endocrine signalling?
If the signalling molecules are released into the bloodstream and travel through the blood to the target cell. Signalling molecule is termed a hormone
When is it synaptic signalling?
If nerve cells release a neurotransmitter into a junction between nerve cells, then the signalling molecule is called a neurotransmitter.
What are the 3 subdivisions of signalling molecules?
- Local chemical mediators
- Hormones
- neurotransmitters
What are the two types of receptors regarding location?
Cell surface receptors Intracellular receptors
When are cell surface receptors used?
When the signalling molecule is hydrophilic so can’t pass the lipid bilayer
When are the receptors intracellular?
When the signalling molecule is hydrophobic so can pass through the lipid bilayer into the cell. Eg steroid hormones, thyroid hormones, oestrogen
What is a receptor
A receptor is a molecule that recognises specifically a
second molecule (ligand) or family of molecules and
which in response to ligand binding brings about
regulation of a cellular process
What is a ligand?
A ligand is any molecule that binds specifically to a
receptor site
When is a ligand termed as an agonist?
When a ligand produces activation of a receptor
When is a ligand termed an antagonist?
When a ligand combines with a receptor site
without causing activation.
It opposes the actions of an agonist
What is the role of receptor in cellular physiology?
- Signalling by hormones/local chemical mediators
- Neurotransmission
- Cellular delivery
- Control of gene expression
- Cell adhesion
- Modulation of the immune response
- Sorting of intracellular proteins
- Release of intracellular calcium stores
What is know about Binding affinity at receptor binding sites?
Affinity of ligand binding at receptor sites is generally
much higher than binding of substrates and allosteric
regulators to enzyme sites
What are receptors classified according to?
Specific physiological signalling molecule (agonist) recognised
What is the sb classification of receptors?
Affinity (tightness of binding) of a series of antagonists
What are the two receptor types of acetylcholine receptors?
Nicotinic Acetylcholine receptor
Muscarinic acetylcholine receptor
What is the agonist for nicotinic acetylcholine receptors?
Nicotine
What is the agonist for muscarinic acteylcholine receptor?
Muscarine
How do you distinguish between a receptor and acceptor?
Receptor
- Silent at rest Agonist
- binding stimulates a biological response
Acceptor
- Operate in absence of ligand
- Ligand binding alone produces no response
Which are the 4 types of receptors which transduce extracellular into intracellular signals?
- Membrane-bound receptors with integral ion channels
- Membrane-bound receptors with integral enzyme activity
- Membrane-bound receptors which couple to effectors through transducing proteins
- Intracellular receptors
Describe how a Membrane-bound receptors with integral ion channels works?
An agonist binding causes an ion channel to open for a particular ion which results in changes in cellular activity.
E.g. nicotinic acetylcholine receptors
Describe how Membrane-bound receptors with integral enzyme activity work?
Transmembrane protein such that when the agonist binds to the receptor site on the outside, a conformational change occurs which activates it and an enzyme converts a molecule into a second messenger which can carry the signal on
What is the advantage of Membrane-bound receptors which couple to effectors through transducing proteins?
Possibility of plasticity as different receptors that recognise the same transducer can be connected to the effector
How do Intracellular receptors work?
- Hydrophobic signals enter the cell through the bilayer
- These receptors bind to transcription factors and modify gene expression.
- Rare
Give 4 examples of Membrane-bound receptors with integral ion channels which belong to the classical receptor family and their ion selectivity
- Nicotinic acetylcholine receptor (nAChR)
- gated Na+, K+ and Ca2+ channel - Gamma amino butyric acid (GABA) receptor
- gated chloride (Cl-) channel - Glycine receptor
- gated chloride (Cl-) channel - Glutamate receptors (NMDA, kainate and AMPA)
- gated entry of Ca2+
Give 3 examples of non classical ligand gated ion channels
- ATP sensitive K+ channel
- P2x purinoceptor
(Na+/Ca2+) - Ryanodine receptor (Ca2+)
Give two examples of Membrane-bound receptors with integral enzyme activity
- Atrial natriuretic peptide (ANP) receptor
- linked directly to guanylyl cyclase
- GTP -> cGMP - Growth factor receptors
(Insulin,
epidermal growth factor (EGF),
platelet-derived growth factor (PDGF))
- linked directly to tyrosine kinase
Describe the process of tyrosine kinase-linked receptors
- AUTOPHOSPHORYLATION - insulin binds to the receptor triggering the. Phosphorylation of the receptor
- Enzyme activation - enzyme binds to phosphotyrosine recognition site which activates enzyme
OR
- TRANSDUCER ACTIVATION - transducer binds to tyrosine - phosphatase receptor. Activated
- ENZYME ACTIVATION -enzyme binds to transducer and becomes activated.
Remember activated = phosphorylated (in this case )
What are there so many phosphorylation sites within transducers in tyrosine kinase linked receptor mechanism?
Insulin has many function: Stimulates glucose storage Inhibition of glycogen breakdown Fat storage Inhibition of Lipolysis
So different signals for many different functions so needs to set off many different regulatory pathways. Each phosphorylation site within transducer are the docking points for each pathway.
Describe the structure of G protein coupled receptors
- Binding domains are within the plane of the membrane
- The g protein coupling domain is intracellular
- Seven transmembrane domains fold to form a cleft into which the ligand binds
Describe the intracellular receptor family
- Receptor held in silent state because of inhibitory protein blocking the DNA binding site
- On binding of hormone, the receptors change conformation so that the inhibitory protein is released and the DNA binding site is exposed
Describe Amplification in cellular signalling
- One ligand binding to a receptor can activate multiple G proteins until the ligand dissociates because after a G protein leaves the activated receptor another can bind
- Each G protein can activate many enzymes e.g adenlyl cyclase which converts ATP to cAMP which activates protein kinase A
- Each protein kinase A can phosphorylate multiple enzymes
- Each of the enzymes can produce thousands of products
- Thus amplification occurs at any steps
Are responses to receptors activation or inhibition?
Responses to receptor activation can lead to cellular activation or inhibition depending on the receptor activated
