General principles of Cell Communication and Intracellular Signalling Flashcards
What are the 3 different types of signalling?
- Autocrine – Hormone is secreted and the target site is located on the secretory cell.
- Paracrine - Hormone is secreted by secretory cell and only targets adjacent cells (due to the limits of diffusion).
- Endocrine - A secretory cell produces then releases a hormone directly into the blood supply to travel to a target cell.
give an example of a specific type of paracrine signalling?
Synaptic signalling- signalling at a junction between two neurones using a neurotransmitter
what is the role of receptors?
Cell releases a substance that act on specific receptors on the surface of the cell
Receptors transduce the response from the cell exterior to the interior and are responsible for producing a biological response.
what is the difference between a 1st and 2nd messenger?
First messenger- the substances that are released by a cell and act on a receptor on another cell (or the same cell in the case of autocrine)
Second messenger- substances produced inside the cell (intracellular) and are responsible for the biological effect inside the cell
what was the purpose of the Otto Loewi experiment?
to examine whether nerve stimuli were transmitted electrically or chemically between cells
what happened during the Otto Loewi experiment?
-In his experiment he used two frog hearts.
-Heart #1 was connected to the vagus nerve and placed in a chamber that was filled with saline.
-This chamber was connected to a second chamber that contained heart #2 so, fluid from chamber #1 was allowed to flow into chamber #2.
-Electrical stimulation of the vagus nerve caused heart #1 to slow down.
-Loewi also observed that after a delay, heart #2 also slowed down.
-From this experiment, Loewi hypothesized that electrical stimulation of the vagus nerve released a chemical into the fluid of chamber #1 that flowed into chamber #2.
-He called this chemical “Vagusstoff”. We now know this chemical as the neurotransmitter – ACh
what are agonists?
compounds that will produce the same effects as the neurotransmitter (mimics it)
what are antagonists?
fit into the active site but has no response – it blocks the effects of the native neurotransmitter
what is the structure of agonists and antagonists?
Agonists and antagonists have to be structurally similar to the in order to fit into the same active site of the receptor, but the other components of the molecule can be distinctly different.
what are acetylcholines antagonists and agonists?
nicotinic effects
muscarinic effects
what is the agonist and antagonist in the nicotinic effects and what do they do?
Agonist: Nicotine - binds to nicotinic acetylcholine receptors (nAChRs) and activates it at the neuromuscular junction (NMJ). Causes Na+ influx which results in muscle contraction.
Antagonist: Curare (arrow poison)- binds to the active site of nAChR at the NMJ (blocking effect of Ach) causing skeletal muscle paralysis.
what is the agonist and antagonist in the muscarinic effects and what do they do?
Agonist: Muscarine- activates M1-M5 receptors (GPCRs). Too much can cause Bradycardia, salivation, bronchospasm, mydriasis (dilation of pupil)
Antagonist: Atropa Belladonna alkaloids (Atropine) Scopolamine, etc.) – Blocks the muscarinic effects
what is the structure of nicotinic AChR?
- Microscopes show little donut like structures that are single Nicotinic AChR
- They are pentameric ion channels- 5 different subunits.
- It is an ion channel- allows Na+ to cross PM
- They have an extracellular domain where ACh binds.
- They also have a transmembrane portion which are alpha helices and an intracellular domain.
what is the mechanism of a nicotinic AChR?
- In the absence of ACh, the gates are in a closed conformation.
- 2 ACh molecules binds to the two extracellular subunits (receptor) - the channel changes conformation and opens and Na+ can travel into cell for depolarisation.
How were biological effects (hormones & neurotransmitters) measured?
Muscle stripe- put into a forced transducer which was linked to a pen that was recording the contraction over a period of time (before and after the drug was applied).
How do you measure ligand binding to a receptor?
- Isolate the desired hormone
- Label the hormone to make it radioactive
- Allow radioactive ligand to bind to the receptor
- Wash away the unbound ligand
- Measure the amount of radioactivity emitted from the remaining ligand- receptor complex
- Radioactivity measure proportional to number of receptors that have ligands bound that are present
- Can also measure affinity (strength of binding) at a concentration of ligand
what is Kd?
concentration of ligand required for 50 % of receptors to be bound with said ligand.
The lower the Kd the higher the affinity
