Types Of Signalling 1

Paracrine
• Chemical synthesised and released from individual cells, not a specialised tissue or gland: Release messenger rather than a specific tissue
• Picked up by receptors on the receiving molecule
• Local effect & Local action: Spread out a short distance by passive diffusion
• Chemical not released into the blood: If levels of chemical got high enough to enter the bloodstream = Would no longer refer to paracrine
but endocrine
EXAMPLES – mast cell
• Small peptide release  Invasion by white blood cells – When activated, mast cells release small peptides  Diffuse locally
signalling
and recruit the invasion by white blood cells – If it wasn’t local, how would white blood cells know where to go?
• Prostaglandin pathway: Prostaglandins  More prostaglandins – When mast cell is activated by infection or injury, it
releases prostaglandins (PGs)  PGs diffuse locally to other cells, inciting them to release PGs as well; PGs released can cause
PGs release from the same cell type (special case of paracrine signalling, AUTOCRINE SIGNALLING)
• Histamine release: Histamine  Arterioles dilation  Increased blood flow – Mast cells respond by releasing histamine 
Diffuse to arterioles where it causes vasodilation  Cause increased blood flow to the affected area; Histamine released increase
permeability in capillaries to proteins (ex: immunoglobulins) – Local otherwise, a small injury would affect the whole system
• Bacterium – Mast cells are activated by infection (Ex: by bacteria) or by injury
• [**MAST CELL = Found in connective tissue all over the body; Secrete histamine in response to injury or infection]
Autocrine
• Chemical released acts on the same cell as released it = Produce “virtuous circle” where there is a build up of chemical = Inflammation
(ex:)
Contact-Dependent
• Involves physical contact between 2 cells – ligand bind to 1 cell attach to receptor on the other cell so adjacent
Types Of Signalling 2
Synaptic
• Used by nerve cells / neurones
• Rapid – fastest form of signalling
• Specific: to target organ = extremely localized delivery
• Information sent electrically (action potentials) and delivered at target chemically
• Long range
• Message reaches end of neurone = Pre-packaged neurotransmitter chemical secreted/released
into cleft = Neurotransmitter binds to sodium channel receptors = Channel open up for a
response, chemical signalling
• At synapse, action potential arrives at presynaptic terminal  Release of neurotransmitter 
Neurotransmitter diffuse across the cleft to its postsynaptic site  Neurotransmitter binds to a
receptor  Action potential
• NEUROTRANSMITTER: generally packed into membrane-bound vesicles EXCEPT Nitric
Oxide as it is lipophilic
Endocrine
• Diffuse, long-distance signalling – Distribute chemical (hormones) through the blood or other fluid
transport
• Release of chemical, hormones, controlled by endocrine gland tissue with several mechanisms
• Only specific cells with appropriate receptors respond
• Remote action (broadcast)
• Secrete in response to signals
• Slower than synapses
Principles Of Signalling
Storing Message Receptor
• Messaging molecule • Detect presence of signalling molecule in the environment = Cause response in
synthesised and stored in cell
vesicles which bud off the • TRANSDUCTION = Whole process of receiving a chemical message and turning
Golgi body then can be stored, it into a cell’s response
fusing with plasma membrane, • AGONIST = Molecule activates a receptor (natural or artificial message or it may
releasing chemical energy be a chemical that is “mistaken” for the natural message) (many drug are agonists)
• ANTAGONIST = Doesn’t activate receptor by stopping them from opening by
STORAGE OF LIPID- binding and blocking instead
SOLUBLE PROCESS VIA RECEPTOR
• Vesicle membranes are lipid bilayers = Lipid bilayer 1.
MESSENGER MOLECULE = Chemical properties of molecule are not
MESSENGER important but has a recognition site on a receptor
offer no resistance to passive diffusion of lipophilic
substances = Don’t keep messenger in vesicles 2. LIGAND BINDING = Site on receptor molecule that recognizes the
• Some synthesised as/when needed chemical messenger so only certain molecules will bind to site
• NITRIC OXIDE: controls vasodilation; produced by the 3. RECEPTOR MOLECULE = Protein usually embedded in the plasma
action of nitric oxide synthetase membrane with the capacity to respond in some way to the arrival of the
• EICOSANOIDS: 20-carbon compounds; produced by chemical ligand
cyclo-oxygenase or lipoxygenase; many important 4. EFFECTOR PATHWAY = By some mechanism, activating the receptor will
actions in body (prostaglandins in inflammation) cause some sort of response in the cell, usually a strig of messages
Response
• The nature of response doesn’t depend on properties of the message but on the
effects of activating the receptor
• Same messenger can lead to different response: Acetylcholine released from
most motor nerve terminals  Activate muscarinic type receptors  Muscle
contraction OR Acetylcholine released from vagus nerve  Activate nicotinic
type receptors  Cause secretion of a substance to slow down the heart rate
Response
 Response evoked by a cell-to-cell signal depends on: Type of
receptor activated, How much signal arrives at cell, Signalling
pathways connected to receptor that is activated G-Protein Receptor
• = Have receptor on cell surface
Ion Channel Membrane-Bound Enzyme 1. Ligand originally closed
• = Integral membrane proteins • = Effector protein embedded directly in plasma membrane 2. Ligand binds to receptor in membrane
with gate originally closed 1. Ligand binds to effector enzyme in the membrane 3. Receptor activates a G-protein (signals indirectly
1. Ligand binds to an ion 2. Direct effect: enzyme causes protein phosphorylation through G-proteins), effector is a separate protein (ion
channel receptor 3. Causes downstream effects – cascade effect of protein channel)
2. Ion channel opens phosphorylation 4. G-proteins interact with ion channel
3. Ions cross the membrane by 5. G-protein gates an ion channel OR G-protein activates a
passive diffusion down second messenger (cyclic AMP, IP3, Calcium ions) –
electrochemical gradient which causes cellular effects
4. Hyperpolarization OR 6. Ions can flood in: membrane potential, signalling by
Depolarization – change in changing ion (indirect) OR through second messenger,
membrane potential (protein affect other proteins in cell causing release in ion for
activation/synthesis) signalling and phosphorylation of other proteins
(direct)
Intracellular Receptor
• = Receptors located inside the cell
(inside nucleus)
1. Ligand diffuses through
membranes to receptors in the
cell/nucleus – lipophilic
2. Receptor activated and cause
mRNA synthesis
3. mRNA makes a protein
4. Protein exerts a cellular effect
Second Messenger Signalling
Second Messenger
• SECOND MESSENGER = Small molecules and ions that relay signals from receptors at the
cell surface to effector proteins
• Are a wide variety of different chemical species (cAMP, IP & DAG, Calcium ions) = Enable
versatility, Range of responses, Signal amplification, Regulated
• Are present in low concentrations until needed  Can be rapidly produced or released when
cells are stimulated = Are controlled temporarily and spatially
Principles Of Second Messenger Signalling
• Variety of signalling pathways = Many receptors respond to a intercellular message by
evoking a cascade of intracellular signals = Second-messenger receptors
1. Receptor embedded in membrane
2. Ligand diffuses and binds to receptor
3. Receptor activated cause second messenger activated inside the cell
4. Second messenger activates a set of downstream signalling pathways via phosphorylation
5. Produce other messages = Evoke cell response
Second Messenger Signalling
• Receptor activated  Downstream signalling are biochemical reactions
• Slower than ions flowing in through ion channel BUT Can mediate long-lasting responses, up to hours
• Downstream effects can be very slow in themselves (turning on mRNA expression)
Calcium – second messenger
• Free intracellular calcium ions accumulate via different pathways from even same receptor
1. Calcium can come in through calcium ion channels in plasma membrane
2. Calcium can come from the activation of second messenger receptors from a different part to plasma
membrane = Release of IP3 = Release of Calcium ions from intracellular stores (ER)
3. 2 routes how to increase intracellular Calcium ions
4. Calcium ions operate through binding to calcium-binding proteins = Change how protein behaves = Effect
G Protein Signalling
 G-protein coupled receptors (GPCR)
 Specific specialised proteins with unique membrane receptor – bind to GTP & GDP
 Span membrane 7 times – 7 alpha transmembrane helices/receptors
 HETEROTRIMETIC = All G-proteins associating with GPCRs: 3 different subunits (alpha, beta, gamma – alpha
& gamma bind to membrane by lipid anchor)
 G-protein coupled to receptor
Signalling Pathway
1. Inactive G-protein = GDP (Guanosine DiPhosphate) binds to alpha subunit
2. Ligand binding to receptor = Signalling molecule binds complementary to
GPCR = Activated G-protein
3. Conformational change of shape
4. Alpha subunit exchanges GDP for GTP
5. G-protein dephosphorylated = Breaks up diffuses to receptor
6. Alpha subunit, G protein, dissociate = Move away from beta and gamma
subunits = Regulate target proteins (enzymes / ion channels)
7. G-protein interacts with target proteins to relay messages via second
messengers
8. Alpha subunit activate membrane-bound ADENYLYL CYCLASE
ENZYME (AC) = ATP (Adenosine Triphosphate) converted into cAMP
(cyclic Adenosine Monophosphate)
9. cAMP acts as second messenger to bind to other proteins = cAMP activates
and phosphorylates PROTEIN KINASE A for signalling
10. Ligand leaves = GTP hydrolysed to GDP (RGS protein can accelerate but
controlled naturally)
• PHOSPHODIESTERASE ENZYME: cAMP  ATP
1. Types of stem cells
2. Cell proliferation = makes lots of cells but same as self-renewal
3. Own stem cell implanted = tumour or cancer probability as might go
to the wrong place in body and proliferates
4. Cells eventually run out of ability to profilerate due ot hey flick limit
so less stem cells available when older (telomere becomes shorter
until chromosomes not protected)
5. Connective tissue proper
6. Lots of collagen fibres = more tensile strength = dense compared to
loose
7. Regular = tendons & ligaments
8. Irregular = Under skin
9. Areolar = directly under epithelial cells
10. Reticular = lymph noeds, spleen
11. Adipose = under skina nd around kidneys and heart for insulation –
fat and important for hormones (control hunger)