M&R Session 6 Flashcards
How can signalling by secreted molecules be subclassified?
Paracrine
Endocrine
Synaptic
How can intracellular signalling occur?
Secretion of signalling molecules
Where adhesion proteins in adjacent cells are in contact
What is paracrine signalling?
Signal molecules act on adjacent cells
What is endocrine signalling?
Signal molecules enter the bloodstream and act on distal tissues
What is synoptic signalling?
Use of neurotransmitter as a signal molecule
How do hydrophilic signalling molecules work?
Bind to cell surface receptors
How do hydrophobic signalling molecules work?
Transported by carrier protein and bind to intracellular receptors in cytoplasm or nucleus
What is a receptor?
A molecule that recognises specifically a second molecule or family of molecules and in response brings about regulation of a cellular process
Describe an unbound receptor.
Functionally silent
What is a ligand?
A molecule that binds specifically to a receptor site
What is an antagonist?
A ligand which binds with the receptor site but does not cause activation
Does an antagonist switch off a receptor?
No. It prevent agonist binding therefore prevents switch on
What is an agonist?
A ligand which binds and causes activation of a receptor
What are the roles of receptors in cellular physiology?
Cell adhesion Signalling by hormones/local chemical mediators Neurotransmission Modulation of immune response Release of intracellular calcium stores Control of gene expression Cellular delivery Sorting if intracellular proteins
How does the binding affinity at receptor sites compare to at enzyme sites?
Generally much higher
What accounts for the difference in affinity b/w receptor and enzyme binding sites?
Ligands generally have to travel much further than substrates and allosteric regulators for enzymes therefore are more diluted
What is KD?
The concentration of ligand required to half fill all available receptors
What are they comparative ranges of affinity for receptor and enzyme binding sites?
Receptor = 10^-9 M to 10^-6 M Enzyme = 10^-6 M to 10^-3 M
How are receptors classified?
Specific agonist
Affinity to a series of antagonists
How are ACh receptors classified?
ACh
Nicotinic/muscarinic
Muscarinic into M1-M5 determined by the antagonists for which they have the highest affinity for
Give the antagonists which the receptors M1-M3 have the highest affinity for respectively.
M1 = Pirenzipine M2 = Gallomine M3 = Hexahydrosiladiphenol
How does an acceptor differ to a receptor?
An acceptor operates in the absence of ligand and ligand binding alone produces no response
Give two examples of acceptor molecules, explaining why they are not receptors.
Dihydrofolate reductase - functions in absence of methotrexate
Sodium channel - modulated by binding of other chemicals and functions w/out anaesthetic
What are membrane-bound receptors w/integral ion channels also called?
Classical ligand-gated ion channels
Describe the structure of nAChR.
5 subunits put -ve residues at mouth of channel
Give 5 examples of membrane-bound receptors w/integral ion channels.
nAChR GABA receptor Glycine receptor Glutamate receptor IP3 receptor
What ions do nAChR permit the passage of?
Sodium
Potassium
Calcium
What is the function of gamma amino butyric acid receptors?
Gated chloride channels which allow membrane hyperpolarisation
What ion movement do glycine receptors control?
Chloride
Give examples of glutamate receptors and state what ionic movement they control.
NMDA
Kainate
AMPA
All allow gated calcium entry
What does inositol 1,4,5-triphosphate allow?
Gated released of calcium from the ER
Give three examples of non-classical ligand-gated ion channels.
ATP-sensitive potassium channel
Purinoceptor
Ryanodine receptor
Describe the structure of ATP-sensitive potassium channels.
A channel pore with an ATP molecule on the intracellular side between 2 transmembrane domains
How does the structure of a purinoceptor relate to that of an ATP-sensitive potassium channel?
The same except for the shape of the channel pore and the location of the ATP molecule on the extracellular side
Describe the structure of a ryanodine receptor.
Four transmembrane domains with calcium and ryanodine linked to the first domain
Give two examples of membrane-bound receptors w/integral enzyme activity.
Atrial natriuretic peptide receptor
Dimeric growth factor receptor
What are ANP receptors directly linked to?
Guanylyl cyclase (GTP –> cGMP)
What are dimeric growth factor receptors directly linked to?
Tyrosine kinase
Describe the mechanism of dimeric growth factor receptors.
Allow phosphorylation of tyrosine for growth
Give some examples of the resultant molecules from activation of dimeric growth factor receptors.
Insulin
Epidermal growth factor
Platelet-derived growth factor