11. Biological Signalling And Receptors Flashcards
What are the 2 ways of intercellular signalling?
Signalling by secreted molecules
Signalling by plasma membrane-bound molecules
What are the 3 subdivisions of signalling molecules?
Local chemical mediators (paracrine)
Hormones (endocrine)
Neurotransmitters (synaptic)
What is a receptor?
Molecule that recognises specifically a second molecule (ligand) or family of molecules and which in response to land binding brings about regulation of a cellular process
In unbound state a receptor is functionally silent
What is a ligand?
Any molecule that binds specifically to a receptor site
What is an agonist?
A ligand which when it binds can produce activation of a receptor
What is an antagonist?
A ligand that combines with a receptor site and does not cause activation, it opposes the actions of an agonist
Acts as a competitive inhibitor
What is the role of receptors in cellular physiology?
Signalling by hormones/local chemical mediators Neurotransmission Cellular delivery Control of gene expression Cell adhesion Modulation of immune response Sorting of intracellular proteins Release of intracellular calcium stores
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
How are receptors classified?
Specific physiological signalling molecule (agonist) recognised
E.g. adrenaline receptors
How are receptors sub-classified?
Affinity (tightness of binding) of a series of antagonists
What are the 2 receptor types of acetylcholine receptors?
Nicotinic
Muscarinic
Difference between acceptor and receptor?
Receptor: silent at test, agonist binding stimulates a biological response
Acceptor: operate in absence of ligand, ligand binding alone produces no response
What are the 4 types of signal transduction?
- Membrane-bound receptors with integral ion channels (fastest)
- Membrane-bound receptors with integral enzyme activity
- Membrane-bound receptors which couple to effectors through transducing proteins (most common)
- Intracellular receptors
Classic receptor family examples
Nicotinic acetylcholine receptor
GABA receptor
Glycine receptor
Non-classical ligand-gated ion channels examples
ATP sensitive potassium channel
Ryanodine receptor
Examples of membrane-bound receptors with integral enzyme activity
Atrial natriuretic peptide receptor (GTP-> cGMP)
Growth factor receptors - insulin, epidermal growth factor
Signalling via tyrosine kinase-linked receptors
Tyrosine residues (receptor) are intracellular
An agonist (insulin) binds to receptor
Tyrosine kinase activated and phosphorylates chain its connected to (receptor)
Causes conformational change
Autophosphorylation then takes place
One route: allows proteins that have phosphotyrosine recognition site in them to come along and bind to receptor, enzyme then active
Second route: receptor is phosphorylated, transducer binds, transducer then phosphorylated, enzyme then binds to transducer and is activated
Membrane-bound receptors that signal through transducing proteins
(Seven transmembrane domain receptors)
Coupled through GTP-binding regulatory proteins (G-proteins) to enzymes or channels
Adrenaline binding to beta-adrenoceptors activates enzyme adenylyl cyclase via a G-protein (Gs)
Acetylcholine binding to M2 muscarinic acetylcholine receptors stimulates potassium channel opening via a different G-protein (Gi)
Examples of G-protein coupled receptors
Bacteriorhodopsin
Beta-2-adrenoceptor
Cellular activation and inhibition
Responses to receptor activation can lead to cellular activation or inhibition depending on the receptor activated
Cardiac pacemaker cells activation and inhibition
Activation: noradrenaline -> beta-1-adrenoceptors -> increased heart rate
Inhibition: acetylcholine -> M2 muscarinic receptors -> slowing of heart rate
Hepatocytes activation and inhibition
Activation: insulin -> stimulates glycogen synthesis from glucose
Inhibition: glucagon -> stimulates glycogen breakdown to glucose
