Session 6 Flashcards
What are three ways in which cells can communicate?
Paracrine
Endocrine
Synaptic
What is paracrine communication?
Adjacent cells are effected within a tissue by local chemical mediators
What is endocrine communication?
Message released into bloodstream and affects a distant cell
What is synaptic communication?
Neurotransmitter crosses a synaptic cleft and binds to receptors on the post synaptic membrane of the target cell
What kind of molecule do cell surface receptors bind?
Hydrophillic, such as insulin and glucagon
What kind of molecule do intracellular receptors bind?
Small hydrophobic signalling molecules (bound to a carrier in blood) bind to intracellular recptors in nucleus or cytoplasm. (Thyroid and steroid hormones)
What is a ligand?
Any small molecule that binds to a receptor site.
What is a ligand called if it produces a response in a receptor?
An agonist
What is an antagonist?
A ligand which binds to a receptor without causing any activation.
What is an agonist which stimulates a receptor but are unable to elicit the maximum cell response called?
Partial agonists
What is the definition of a receptor?
A molecule which specifically recognises a ligand or family of ligands and which, in response to ligand binding brings about regulation of a cellular process. In the unbound state, a receptor is functionally silent.
What are the 8 roles of receptors?
- 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 an acceptor?
A molecule whos basic function can be carried out without the interaction of a ligand.
What are the two types of acetylcholine receptors?
Nicotinic and muscarinic
What are the three muscarinic receptors, and their antagonists?
M1 Pirenzipine
M2 Gallamine
M3 Hexahydrosiladiphenol
What is a ligand?
Definition: any molecule that binds specifically to a receptor site
What are receptors classified according to?
Which specific physiological signalling molecule (agonist) recognised
How are receptors subclassified?
By its affinity to a series of antagonists
What are the similarities between receptor binding and active and regulatory sites of enzymes?
- Specific binding
- Specificity shape related
- Specificity of binding confers specificity to the regulation of processes by ligand binding
- Binding reversible
- Ligand binding to a receptor and regulator binding to enzyme allosteric sites induce a conformational change in activity
- No chemical modification of ligand in receptor binding sites or enzyme regulatory sites
What are the differences between receptor binding and active and regulatory sites of enzymes?
- The affinity of ligand binding > binding of substrate and regulators to enzyme sites * Ligand bound to a receptor site is not modified chemically whereas substrate is converted to product by an enzyme
Explain how membrane bound receptors with intergral ion channels have an effect
- Agonist binds to ligand-gated ion channels > conformational change > gated channel opens > permits flow of ions down an electrochemical gradient > signal transduced into an electrical event
What is the subunit structure of a classical ligand gates ion channel family?
- Similar pentameric subunit structures
- E.g. nicotinic acetylcholine receptors (nAChR), GABA receptors, glycine receptors (GlyR)
- Subunits have four transmembrane domains – M2 forms the lining to the channel pore
Describe the activation of membrane bound receptors with intergral enzyme activity
- Agonist binds to extracellular domain > conformational change > activation of intrinsic enzyme e.g. tyrosine kinase-linked receptors
How are tyrosine kinase linked receptors operated?
- Binding of hormone to extracellular domain > activation of protein kinase activity in the cytoplasmic domain of the receptor protein kinase activity
What is the effect of tyrosine kinase linked receptor activation?
Autophosphorylates tyrosine residues on the cytoplasmic domain of the adjacent receptor
What are phosphorylated tyrosine residues recognised by?
o Transducing proteins
o Directly by enzymes containing phosphotyrosine recognition sites
How is does phosphorylated tyrosine activate shizzle?
- On association with receptor or transducing protein > effector enzymes become activated allosterically > transduce message into an intracellular event
Describe structure of membrane-bound receptors which couple to effectors through transducing proteins
- Seven transmembrane domains receptors (7TMDR) couple to effector molecules via G-proteins
What are the effectors of membrane-bound receptors which couple to effectors through transducing proteins
o Adenyl cyclase (ATP > cyclic AMP)
o Ion channels e.g. Ca2+ and K+ channels
What are membrane-bound receptors which couple to effectors through transducing proteins used by? (4)
o Muscarinic receptors
o Dopamine receptors
o Peptide receptors
o Purine receptors e.g. ATP
Describe the four roles of intracellular receptors
- Hydrophobic ligands e.g. steroid and thyroid hormones
- Bind to monomeric receptors in the cytoplasm or nucleus
- Receptors stabilised in resting state by association with heat shock or chaperone proteins
- Activated receptors dissociates from the chaperone proteins and translocates to the nucleus > regulates gene expression
Define amplification
- Cascade event
- Binding of a chemical signal molecule to a single receptor can cause the modification of hundreds or thousands of substrate molecules
Define cellular activation and inhibition
- Responses to receptor activations can lead to either cellular activation or inhibition
Give an example of cellular inhibitionv
o E.g. noradrenaline binding to B1 adrenoreceptors in cardiac pacemaker cells > increased heart rate / ACh acting on M2 > decreased heart rate
