Flashcards in Lecture 6: Receptors and Signal Transduction Mechanisms Deck (41)
Long distance communication. A hormone carried to the blood to a distinct target cell where it has effect.
A secretory cell releases signalling molecules to an adjacent target cell, activating receptors on this cell. Could be across a synapse. Must have a neighbour for this type of signalling
A cell releases a signalling ligand that feeds back to the cell that released it and binds to receptors.
Signalling by plasma membrane attached proteins
The ligand is attached to one cell and binds to a receptor on an adjacent cell. The cells are conjoined by this arrangement.
For a drug to have selective action on a cell it muster interact with:
A discrete target (receptor) on that cell
Receptors (what they are made of, where they are located)
Made of protein
Typically at the cell surface but also nuclear membrane proteins and even enzymes can act as receptors.
Binding of drugs to receptors results in (3):
-Conformational changes in receptor.
-Transduction of the signal via alterations in cytosolic metabolism
-Changes in cell function and gene transcription
Where endogenous ligands bind a receptor. Most drugs mimic endogenous ligands, so they will also bind here. The receptor site that binds the neurotransmitter.
A distinct site on a receptor that the endogenous ligand doesn't bind to. Can cause a change in the orthosteric site.
Any endogenous neurotransmitter. Something that is recognized by and binds to a receptor.
The 5 ways in which drugs can intervene in neuronal receptor signalling (neuronal modulation)
1. Synthesis of transmitter in presynaptic nerve terminal
2. Release of transmitter and transport to the target cell
3. Detection of the signal by a specific receptor protein
4. Change in cellular metabolism triggered by the receptor signalling molecule complex
5. Removal of the signal, terminating the cellular response.
-Ligand gated ion channel (LGIC)
-Receptor tyrosine kinases (RTK)
Another term for LGIC
-Present on cell membrane
-Composed of 3-5 subunits and a central aqueous channel
-Central pore requires binding of a ligand to change the conformation of the channel so that ions can pass through.
-Involved in fast neurotransmission.
-If the charge across the membrane is a favourable gradient, the ions will flow. NOT Voltage gated
Things that pass through LGICs
Na+, Ca2+, Cl-
Examples of LGICs
-Nicotinic ACh (non-selective for sodium and calcium)
How do LGIC and voltage gated ion channels differ?
While LGIC need favourable membrane potential for ions to flow through, they are gated by the binding of a ligand. VGICs don't need this.
Nicotinic Receptor Signalling
-ACh is released and binds to its receptor
-Receptor is able to pass sodium ions into the cell with the gradient
-Small depolarizations in the muscle sum and cause action potentials and the muscle contracts.
-Membrane bound enzyme
-Hydrolyzes released ACh, producing choline and acetate that are recycled.
Where are LGICs that respond to ACh normally found?
-Nerve synapses at neuromuscular junctions.
Most drugs are targeted toward
GPCRs (at least 50%)
-Family A: Rhodopsin-like
-Family B: Glucagon/ VIP/Calcitonin
-Family C: Metabotropic glutamate and chemosensor
-7 transmembrane domains
-N terminal that is frequently extracellular
-Intracellular carboxy terminal
Function of IL3 loop
Slightly longer than others; has a function in binding downstream signalling molecules i.e. G-proteins
Important in decreasing association of the receptor with the G-protein
The G protein is inactive when bound to
When an agonist that stabilizes the signalling form of the receptor binds, it allows:
Association with the G protein and the removal of GDP, so that it can bind GTP. The heterotrimeric g protein breaks apart, and the G-alpha subunit will signal downstream proteins.
Effectors commonly associated with GPCRs (5)
-Phospholipases C & A2
Orphan receptors and ligands
Things we see in research but haven't been able to put them into a class because we dont know how they function.