Physiology 3140A Lecture Notes - Lecture 1: Vascular Endothelial Growth Factor, Autocrine Signalling, Paracrine Signalling

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Physiology 3140
Dr. Rylett
Lecture 1
Multicellular organisms: made up of cells
- Cells communicate by sending and receiving signals
o Can be hormones
o Can be neurotransmitters
o Can be other types of chemicals that they release
- Cells can also communicate with physical things
o Photons of light
o Heat
o Cold
o Vibration
o Sound
o These can all be considered as a form of ligand bc receptors take this and use it as a
signal to release signals
- Signals originate from:
o Environment
o other cells
- enable us to stay alive
Forms of Intercellular Signalling
- contact dependent signalling
o critical for things like:
development of tissues
synaptic plasticity
in our brains, our synapses are always modifying themselves (you lose
some and gain some) in response to something you are doing
this all takes place by modifying interactions bw cells
some of that will relate to substances present on target cells and the
signalling cell will be able to receive that
ex: integrins(green molecule)
ex: efrin (green molecule)
the target cell will express a cell surface signal and some
sort of other cell (ex: signalling cell) will come up and
have a ligand to interact with that
green is receptor, red is ligand
o Signaling molecules remain bound to surface of signaling cell
o Activate target cells that come into contact with signaling cell
o target cell will express some type of signal and another cell will come up
and have a type of ligand to interact with that sf
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- endocrine signalling
o long distance signaling
o endocrine cells release hormones into the bloodstream - transported throughout body
(signaling over long distances) through circulatory system
o hormones act on target cells that express a receptor for that specific ligand
o hormone signaling is a relatively slow (minutes-hours-days)
bc sometimes they do nuclear changes which involves gene expression
modification which can take long
o it will find target cells based on the receptor on the target cells
o
o engage a number of different tissues or organs in body
- Paracrine Signalling
o Para = near
o secreted signaling molecules act as local mediators that impact target cells only in the
immediate environment
o examples of ligands:
platelet-derived growth factor (PDGF)
wound healing
fibroblast growth factor (FGF)
cell growth, differentiation
o local mediator interacts with cells in that immediate environment (so now were looking
at within a tissue, instead of multi-organ)
o endocrine signaling may engage in a number of diff tissues and organs in body but
paracrine would engage a local environment in one tissue (bc they are local mediators)
o a characteristic of the ligand that would dictate that this is a local event:
ligands (local mediator) that have a short half life (degrade spontaneously or get
broken down by enzyme or it may bind to receptors on cell surface and actually
be taken up into the cells)
important characteristic of local mediator that can determine whether it acts
locally or whether it can be distributed throughout the body
o hormones that act further away (in other tissues of the body) have to be stable enough
to be able to get out into the blood, travel in the blood, get to some target organ further
away so they have to be stable enough to not be degraded immediately by some sort
of enzyme or taken up by cell (IMPORTANT FOR EXAM)
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- Autocrine Signalling
o Auto=self
o Way for cell to signal to itself that something is happening
o So cell that releases the thing also has the receptor for that ligand
o So the purpose of the ligand receptor interaction in this case is to tell that cell that
release the ligand that it did its job in a certain way
o This cell may be releasing molecules (ex: hormone) that is going away from those cells
(could be acting as a paracrine or even endocrine effect) but the cell that released it in
the first place also has autocrine signalling this way the cell knows that it did its job
o it doesn’t have to be the same molecule, it can be a release of substances from the
granules (there can be multiple different substances in the granules of cells some of
them could be endocrine factors and some of them autocrine factors)
o or you can have a group of cells, where a whole bunch of the cells begin to release the
same cells
o but the point is to: signal back and tell cell that the job has been done
o cell releases a signaling molecule that acts back upon receptors expressed on its own
surface to control its activity
o examples of ligands:
cytokine interleukin-1 in monocytes
vascular endothelial growth factor (VEGF) in cancer cells
o cell that is releasing it also has those receptors: so cell knows it did its job properly
- Synaptic signalling
o Specialized form of signalling they are specialized nerve cells that signal to target cells
(that sometimes can be very far away)
o regulates long distance communication
o there is a long axon that directs the message far away
o allows for long-term adaptive changes required for behavioral responses to
environmental cues
o neurons (nerve cells) extend long axons to communicate
o axons contact each other at synapses
o rapid signaling the info is out there, AP is happening and rapid synaptic
release and rapid communication
what happens in the target cell may not be rapid but the
communication (ligand to receptor) part is rapid
this is different from for ex: endocrine signaling which is slow
o its done with specialized nerve cells that signal to target cells that can be
far away
o one given neuron can communicate with more than one target cell
(sometimes axons can have dozens of synaptic connections)
o each target cell has more than one synaptic signal as well (some may be excitatory or
inhibitory and its the balance bw these events that determine signal)
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Document Summary

Cells communicate by sending and receiving signals: can be hormones, can be neurotransmitters, can be other types of chemicals that they release. Cells can also communicate with physical things: photons of light, heat, cold, vibration, sound, these can all be considered as a form of ligand bc receptors take this and use it as a signal to release signals. Signals originate from: environment other cells enable us to stay alive. Cells respond to specific combinations of extracellular signals cell signaling contributes to: regulation of metabolic processes, cell growth, cell differentiation, cell migration, cell death (apoptosis) if cell is deprived of appropriate survival signals. Now you have a situation where you have more inputs. So with all these diff hormones and other signals coming in, it may stimulate the cell to grow and divide for example. Or you may get different ones (ex: f and g coming in too) which can lead to differentiation of the cell.

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