Intercellular Communication

and Signal Transduction

Disclaimer: This study set on signal transduction and intercellular communication is
based on lecture PowerPoints and my own research. It is intended to complement
your studies and should not be considered a primary source. Always refer to your
course materials and textbooks for comprehensive information.
Signal Transduction:

• Definition
• Process by which incoming signals
conveyed to target cells where they are
transformed to cellular response
• Goal
• To define the mechanisms that cells,
tissues and organisms use to respond to
physiological and environmental stimuli
• Mechanism
• During process, extracellular signal is
transduced (converted/changed) to a form
to modify intracellular activity to
accomplish desired outcome
Table summarizing communication between cells.

Intercellular Communication

Direct Indirect

Linking of Surface
Gap Junctions Paracrines Hormones Neurohormones Neurotransmitters
Receptors
Direct Intercellular Communication

Involves
physical •Gap Junctions
contact
between •Linking of Surface
interacting Receptors
cells
Gap junctions

Overview:
• Function: Direct intercellular communication via small ions and molecules.
• Structure: Connexons (6 protein subunits) form tunnels between cells.
• Location: Abundant in cardiac and smooth muscle; also, in non-muscle
tissues.
Key Points:
• Connexons: Bridge cytoplasm of neighbouring cells.
• Electrical Signals: Enable synchronized muscle contractions.
• Nutrient Passage: Allow nutrients to pass between cells (e.g., glucose,
amino acids).
Transient linking of cell surface
receptors

• Specialized Markers: Immune cells have specialized markers on their

surface membranes.
• Direct Linking: These markers allow direct linking with other cells that have
compatible markers for transient interactions.
• Phagocyte Function: This mechanism enables phagocytes to recognize and
selectively destroy undesirable cells, such as cancer cells, while sparing the
body’s healthy cells.
Indirect Intercellular Communication

Release and Action: These

Chemical Messengers: Specific
Commonality: This is the most messengers are released into the
signal molecules are synthesized
common form of intercellular extracellular fluid (ECF) upon
by controlling cells to serve specific
communication. appropriate stimulation and act on
functions.
target cells.

Receptors: Cells have thousands

to a few million receptors, with Genomic
Receptor Binding: The chemical hundreds to 100,000 receptors for Importance: Approximately 5% of
messenger binds with a specific the same messenger. Different cell the human genome codes for the
receptor on the target cell to fulfil types have distinct combinations of synthesis of membrane receptors,
its effects. receptors, allowing individual highlighting the importance of this
reactions to various chemical communication method.
messengers.

Types of Messengers: There are

four different types of chemical
messengers, which differ in their
source, distance, and means of
reaching their destination.
Paracrines:

• Local Messengers: Paracrines are local chemical messengers that

exert their effects only on neighbouring cells in the immediate
environment of the secretion site.
• Distribution: They are distributed by simple diffusion within the
interstitial fluid, with actions restricted to short distances.
• Inactivation: They do not reach significant quantities in the blood
due to local enzymes that inactivate them.

Examples and Functions:

• Histamine: Released from connective tissue cells during an
inflammatory response in invaded or injured tissue. It dilates
blood vessels to increase blood flow to the tissue.
• Differentiation: Paracrines are differentiated from chemicals that
influence neighbouring cells after being non-specifically released
during cellular activity. For example, elevated CO2 in exercising
muscle promotes blood vessel dilation to meet the metabolic
demand of active tissue, but since CO2 is released by all cells and
not specifically for this response, it is not considered a paracrine.
Neurotransmitters

Communication: Neurons communicate with cells by

releasing neurotransmitters.

Short-Range Messengers: These are short-range

chemical messengers stimulated by electrical signals
(action potentials).

Diffusion: Like paracrines, neurotransmitters diffuse from

the site of release to act on adjoining target cells
(muscles, neurons, glands).

Electrical and Chemical Signals: Neurons carry

electrical signals along the length of the axon, but the
chemical messenger released at the axon terminal acts at
a short range.
Hormones

• Long-Range Messengers: Hormones are long-

range chemical messengers secreted into the
blood by endocrine glands.
• Transport and Action: The blood carries these
messengers to various sites in the body, where
they exert effects on target cells far from the
release site.
• Specificity: Only target cells with specific
membrane receptors for a hormone will respond
to it. Non-target cells are not influenced by these
hormones.
Neurohormones
• Secretion: Hormones secreted by neurosecretory neurons.
• Response to Signals: Neurosecretory neurons respond to and conduct
electrical signals.
• Release Mechanism: Instead of directly innervating target cells, these
neurons release the messenger into the blood upon stimulation.
• Distribution: The neurohormone is then distributed through the blood to
distant target cells.

Example: Vasopressin (ADH):

• Production: Produced by neurons in the brain.
• Function: Regulates physiological sodium and water balance.
• Response to Stimuli: Increased osmolality or decreased blood
volume/pressure triggers thirst.
• Kidney Function: Promotes water conservation by the kidneys during urine
formation.

Comparison:
• Neurosecretory Neurons vs. Normal Neurons: Neurosecretory neurons
release blood-borne chemical messengers, while normal neurons secrete
short-range neurotransmitters into confined spaces.
Neurotransmitters vs. Neurohormones

Feature Neurotransmitters Neurohormones

Secretion Source Neurons Neurosecretory neurons

Mode of Transmission Released into synaptic cleft Released into the bloodstream

Local target cells (e.g., muscles,

Target Cells Distant target cells
neurons, glands)

Range of Effect Short-range Long-range

Stimulated by electrical signals Respond to and conduct

Response to Signals
(action potentials) electrical signals

Example Acetylcholine, dopamine Vasopressin (ADH)

How do chemical messengers cause the right
response?

Lipid-Soluble Messengers: Water-Soluble Messengers:

Cholesterol-derived steroid hormones. Cannot enter cells due to poor solubility in
• Enter cells via lipid bilayer. lipid bilayer.
• Bind to intracellular receptors or nuclear • Bind to specific receptors on cell surface.
receptors to initiate response. • Protein hormones (delivered by blood) and
neurotransmitters (released from nerve
endings).
How do chemical messengers cause the right
response?
Effects of binding:
1. Membrane transport
2. Secretion
3. Metabolism
4. Contraction
5. Division
6. Differentiation
 How do chemical messengers cause
the right response?

Intracellular Response
Opening/closing
• Mechanisms of Intracellular Response chemically gate receptor
1. Opening/Closing Chemically Gated Receptor Channels: channels
o Messenger binding causes ion channels to open or close,
altering the cell’s electrical state. Activating receptor
enzymes
2. Activating Receptor Enzymes:
o Messenger binding activates enzymes associated with the Activating 2nd messenger
receptor, triggering a cascade of intracellular events. pathways via G-protein-
coupled receptors
3. Activating Second Messenger Pathways via G-Protein-Coupled
Receptors:
o Messenger binding activates G-proteins, which then
activate second messengers inside the cell, leading to
various cellular responses.
Intracellular Response
Opening/closing
chemically gated
receptors channels

Activating receptor
Tyrosine Kinase Pathways
enzymes
Intracellular Response

Adenyl Cyclase (cAMP)

Activating 2nd messenger
pathways via G-protein-
coupled receptors
Phospholipase-C (IP3 &
DAG)
 Chemically Gated Receptor Channels

• Function: Extracellular messengers open/close these channels.

• Mechanism:
• Receptor acts as an ion channel.
• Binding of messenger to receptor-channel opens/closes the
channel.
• Example: Neurotransmitter binding in synaptic membranes.
• Result: Movement of ions across the membrane generates electrical
signals.
• Post-Response:
• Messenger is removed, and channels close.
• Ions are returned to their original location by special membrane
carriers.
Intracellular Response
Opening/closing
chemically gated
receptors channels

Activating receptor
Tyrosine Kinase Pathways
enzymes
Intracellular Response

Adenyl Cyclase (cAMP)

Activating 2nd messenger
pathways via G-protein-
coupled receptors
Phospholipase-C (IP3 &
DAG)
Receptor enzymes
• Function: Relay signals inside the cell via protein kinases.
• Mechanism:
• Phosphorylation: Protein kinases phosphorylate target
proteins, changing their shape and function.
• Signal Transduction: Can involve single or multiple steps
(cascade).
• Example: MAP-Kinase Cascade.
Receptor
Enzyme
example:
MAP-Kinase
Cascade

Focus on that which is

circled in red, the aligning
examples are for
elaboration.
 Protein kinases activated by binding of
signalling molecule to surface receptor via 2
Receptor ways:
• Tyrosine Kinase Pathway: Direct
phosphorylation of proteins.
enzymes • Second-Messenger Pathway: Involves G-
protein-coupled receptors.
Intracellular Response
Opening/closing
chemically gated
receptors channels

Activating receptor
Tyrosine Kinase Pathways
enzymes
Intracellular Response

Adenyl Cyclase (cAMP)

Activating 2nd messenger
pathways via G-protein-
coupled receptors
Phospholipase-C (IP3 &
DAG)
 Tyrosine Kinase Pathway
Simplest of the two main pathways.
• Receptor acts as an enzyme (receptor-enzyme).
• Possesses a protein kinase site on the cytoplasmic portion.
Mechanism:
• Activation: Binding of a signalling molecule activates the receptor’s kinase activity.
• Phosphorylation: The receptor phosphorylates tyrosine residues on itself and other
proteins.

1. Extracellular Messenger Binding:

o An extracellular messenger (signal molecule) binds to the receptor-enzyme on the cell
surface.
2. Receptor Activation:
o The receptor, which has a protein kinase site on its cytoplasmic portion, gets activated
upon binding of the messenger.
3. Phosphorylation:
o The activated receptor phosphorylates tyrosine residues on itself and other proteins.
This phosphorylation changes the shape and function of these proteins, activating
them.
4. Signal Transduction Cascade:
o The phosphorylated proteins (active proteins) then activate other proteins in a cascade,
passing the signal along to designated proteins that carry out the desired cellular
response.
5. Cellular Response:
o The final active designated proteins bring about the cellular response, such as changes
in gene expression, metabolism, or cell division.
Tyrosine kinase pathway
(defective insulin signalling)

• Example: Defective Insulin Signalling:

• Increased: IRS-1 serine
phosphorylation.
• Decreased: IRS-1 tyrosine
phosphorylation, GLUT 4, PI3-Kinase.
• Increased: Ser/Thr cascade, DAG,
ROS, PKC.
• Result: Elevated plasma glucose and
fatty acids.
Intracellular Response
Opening/closing
chemically gated
receptors channels

Activating receptor
Tyrosine Kinase Pathways
enzymes
Intracellular Response

Adenyl Cyclase (cAMP)

Activating 2nd messenger
pathways via G-protein-
coupled receptors
Phospholipase-C (IP3 &
DAG)
Second Messenger
Pathway
• Initiation:
• Binding of the first messenger to a G-protein-coupled receptor
(GPCR).
• GPCR is a three-part molecule (α/β/γ).
• Inactive when bound to GDP; active when bound to GTP.
• Has 7 membrane-spanning domains with extracellular N
terminus and cytoplasmic C terminus.
• Mechanism:
• Activation: Binding of the first messenger activates the G-
protein.
• Effector Protein: G-protein alters the activity of a nearby
membrane protein (effector protein).
• Second Messenger: Effector protein increases the
concentration of an intracellular messenger (second
messenger).
• Signal Cascade: Second messenger sends signals through a
cascade, changing the shape and function of designated
proteins via phosphorylation.
Second Messenger Pathway

Examples of Second Messengers:

• Ca²⁺: Binds to calmodulin and other proteins, altering enzyme activity, exocytosis, muscle contraction, cytoskeletal movement, and channel opening.
• IP₃: Releases Ca²⁺ from intracellular stores, affecting enzyme activity, exocytosis, muscle contraction, cytoskeletal movement, and channel opening.
• DAG: Activates PKC, which phosphorylates proteins.
• cAMP: Activates PKA, binds to ion channels, phosphorylates proteins, and alters channel opening.
• cGMP: Activates PKG, binds to ion channels, phosphorylates proteins, and alters channel opening.

G proteins are linked to amplifier enzymes (effector proteins):

• Adenyl Cyclase: GPCR (cAMP).
• Guanyl Cyclase: Receptor enzyme (cGMP).
• Phospholipase C: GPCR (calcium).

Effects of G-Protein Activation:

• Opens ion channels.
• Alters enzyme activity.
Intracellular Response
Opening/closing
chemically gated
receptors channels

Activating receptor
Tyrosine Kinase Pathways
enzymes
Intracellular Response

Adenyl Cyclase (cAMP)

Activating 2nd messenger
pathways via G-protein-
coupled receptors
Phospholipase-C (IP3 &
DAG)
GPCR: Adenylyl
Cyclase-cAMP
1. Signal Molecule Binding:
o A signal molecule binds to a G-protein-coupled receptor
(GPCR), activating the G protein.
2. Activation of Adenylyl Cyclase:
o The activated G protein turns on adenylyl cyclase, an amplifier
enzyme.
3. Conversion to cAMP:
o Adenylyl cyclase converts ATP to cyclic adenosine
monophosphate (cAMP).
4. Activation of Protein Kinase A:
o cAMP activates protein kinase A (PKA).
5. Phosphorylation and Cellular Response:
o PKA phosphorylates other proteins, leading to a cellular
response.
GPCR: Adenylyl Cyclase-cAMP

• Effects of Activating the cAMP Pathway (depending on cellular location and cell
type):
• Modifies heart rate.
• Formation of female hormones in ovaries.
• Breakdown of stored glucose in the liver.
• Control of water conservation in kidneys.
• Perception of sweet taste in taste buds.
GPCR: Guanyl Cyclase-
cGMP Pathway
1. Signal Molecule Binding:
o A signal molecule binds to a G-protein-coupled receptor
(GPCR), activating the G protein.
2. Activation of Guanyl Cyclase:
o The activated G protein turns on guanyl cyclase, an amplifier
enzyme.
3. Conversion to cGMP:
o Guanyl cyclase converts GTP to cyclic guanosine
monophosphate (cGMP).
4. Activation of Protein Kinase G:
o cGMP activates protein kinase G (PKG).
5. Phosphorylation and Cellular Response:
o PKG phosphorylates other proteins, leading to a cellular
response.
GPCR: Guanyl Cyclase-cGMP
• Effects of Activating the cGMP Pathway (depending on cellular location and cell type):
• Low Ca²⁺ Levels: Activates the pathway.
• High Ca²⁺ Levels: Inhibits the pathway.
• Cellular Effects:
• Drives adaptive/developmental changes.
• Causes relaxation in smooth muscle tissue.
• Increases cGMP, contributing to excessive neuron excitability and locomotor
activity.
• Stimulates presynaptic glutamate release.
Intracellular Response
Opening/closing
chemically gated
receptors channels

Activating receptor
Tyrosine Kinase Pathways
enzymes
Intracellular Response

Adenyl Cyclase (cAMP)

Activating 2nd messenger
pathways via G-protein-
coupled receptors
Phospholipase-C (IP3 &
DAG)
GPCR: Phospholipase C
Pathway
1. Signal Molecule Binding:
o A signal molecule activates the receptor and the
associated G protein.
2. Activation of Phospholipase C (PL-C):
o The activated G protein turns on phospholipase C, an
amplifier enzyme.
3. Conversion to DAG and IP₃:
o PL-C converts membrane phospholipids into diacylglycerol
(DAG) and inositol triphosphate (IP₃).
4. Activation of Protein Kinase C (PK-C):
o DAG activates protein kinase C.
5. Release of Ca²⁺:
o IP₃ causes the release of Ca²⁺ from intracellular organelles.
Second Messenger
Pathway
Post-Response Mechanisms:
• GTP to GDP Conversion: Alpha (α) subunit cleaves off a
phosphate, converting GTP to GDP.
• Degradation of cAMP/cGMP: Phosphodiesterases degrade
cAMP and cGMP.
• Removal of Phosphate Groups: Protein phosphatases
remove added phosphate groups, shutting off the signal
transduction pathway.
• Protein kinases are not always active.
• Protein phosphatases are always active.
• Removal of phosphate groups from activated
proteins allows phosphates to shut off signal
transduction pathway
Second Messenger Pathway

Neurotransmitter Function: First Messenger Removal:

Most neurotransmitters function via Depending on cell type:
second-messenger systems: • First messenger is released from the target
Fast Synapses: Rapid response by changing cell and degraded by the liver or excreted in
conformation of chemically gated receptor urine.
channels, altering membrane permeability • Both first messenger and receptor are
and ion fluxes. removed by receptor-mediated
Slow Synapses: Second-messenger- endocytosis.
mediated responses (e.g., serotonin).
Second
Messenger
Pathway
• Receptor-Mediated
Endocytosis:
• Involves the
internalization of the
receptor and its
bound ligand.
Second Messenger Pathway

Variability in Response: Clinical Relevance: Importance:

Activation of intracellular ½ prescribe drugs are GPCRs. Second-messenger systems are
signalling pathways by second Used in frugs for: widely used throughout the
messengers is similar among body, especially in signalling of
different cells, but the response • High blood pressure water-soluble hormones.
varies depending on cell (hypertension).
specialization, NOT the • Congestive heart failure
mechanism. (CHF).
• Suppression of stomach acid.
• Asthma (opening airways).
• Inhibition of histamine-
induced allergic reactions.
 Hormonal communication

For the sake of this block hormonal communication will be determined by two properties of hormones:
Solubility and Structure.
Hormonal communication
Peptides

Hydrophilic Proteins

Amines (catecholamines
& Indoleamines)
Hormones

Thyroid (catecholamines)

Lipophilic

Steroids
 Hormonal
Communication
Hydrophilic Hormones (“H₂O loving”):
• Composition: Majority are peptides or proteins made up of specific amino
acids (a’a) arranged in chains.
• Short a’a chains → peptides.
• Long a’a chains → proteins.
• Amines (a’a derivatives):
• Hydrophilic: Catecholamines and indoleamines.
• Lipophilic: Only thyroid hormones.
• Examples:
• Catecholamines (from tyrosine) → Adrenal medulla:
• Epinephrine (adrenaline).
• Indoleamines (from tryptophan) → Pineal gland:
• Melatonin.
• Neurotransmitters:
• Dopamine (catecholamine).
• Serotonin (indoleamine).
 Hormonal (hydrophilic) processing

1. Synthesis:
o Large preprohormones (precursor proteins) are synthesized by ribosomes on the rough ER.
2. Packaging in Smooth ER:
o Smooth ER packages proteins/hormones into transport vesicles that bud off and migrate to
the Golgi complex.
3. Modification:
o During the journey to the Golgi complex, preprohormones are modified into active hormones.
4. Fusion with Golgi Complex:
o Transport vesicles from the ER fuse with the Golgi complex to release their contents.
5. Packaging in Golgi Complex:
o The Golgi complex packages the finished product into secretory vesicles, which are stored in
the cytoplasm until a signal triggers their secretion.
6. Secretion:
o On signal, the secretory vesicle fuses with the plasma membrane to release contents into the
blood via exocytosis.
7. Lysosome Formation:
o Lysosomes also bud off from the Golgi complex.
Hormonal
Communication
Lipophilic Hormones (“lipid loving”):
• Solubility: Soluble in lipids.
Types:
• Thyroid Hormones: Triiodothyronine (T₃), Thyroxine (T₄).

• Steroid Hormones: Neutral lipids derived from cholesterol.

• Adrenal Cortex Hormones: Cortisol.
• Sex Hormones: Testosterone (males), Estrogen (females).

• Properties:
• Solubility properties determine:
• How the hormone is processed by the endocrine cell.
• How the hormone is transported in blood.
• How the hormone exerts its effects on the target cell.
Lipophilic and steroidal hormone processing
Cholesterol is the precursor of all steroid hormones.
• Synthesis involves a series of enzymatic reactions.
• Modifications to the basic cholesterol molecule determine the type and position of side groups attached.
Steroidogenic Organs
• Each conversion of cholesterol to a specific steroid hormone requires numerous enzymes.
• Produce only the steroid hormones for which they have a complete set of necessary enzymes (e.g., cortisol in the adrenal cortex).
Characteristics of Steroid Hormones
• Cannot be stored like peptide hormones.
• Immediately diffuse through the plasma membrane once formed to enter the blood.
• Only cholesterol is stored in significant amounts within steroidogenic cells.
• The rate of steroid hormone secretion is controlled by the rate of synthesis, unlike peptide hormones, which are regulated by the
release of pre-synthesized stored hormone.
Post-Secretion Modifications
• After secretion into the blood, certain steroid hormones undergo further changes within the blood or other organs, becoming more
potent or forming different hormones.
 Lipophilic vs steroid hormone processing

Aspect Lipophilic Hormones Steroid Hormones

Nature Hydrophobic, can cross cell membranes easily Derived from cholesterol, hydrophobic

Produced in steroidogenic organs through enzymatic

Synthesis Often synthesized from cholesterol or other lipids
modifications of cholesterol

Cholesterol is stored in cells; hormones synthesized on

Storage Not stored in significant amounts; synthesized on demand
demand

Transport in Blood Bound to carrier proteins Bound to carrier proteins

Receptors Intracellular (cytoplasmic or nuclear) Intracellular (cytoplasmic or nuclear)

Directly influence gene expression by binding to DNA and Directly influence gene expression by binding to DNA and
Mechanism of Action
regulating transcription regulating transcription

Examples Thyroid hormones (T3 and T4) Cortisol, Estrogen, Testosterone

Hormonal Transportation
Activity and Endocrine Function Chemical Properties
General Transport: Catecholamines:
Inactivation: Maintenance: and Transport:

Transported via blood to Only the small, unbound Free Hormone Pool: Approximately 50% Chemical properties
target. portion of lipophilic Refers to the small circulate as free dictate how hormones are
hormones is active and fraction of hormones that hormones, and 50% are transported in blood and
can cross capillary walls. are not bound to proteins bound to albumin (a how they can be
Hydrophilic hormones: in the blood. plasma protein). introduced for therapeutic
Dissolve directly in blood. purposes.
Once a hormone interacts Importance: Only these
with its target cell, it is free hormones can enter The significance of protein
Lipophilic hormones inactivated or removed. cells and exert their binding for water-soluble The digestive system does
(including thyroid biological effects. hormones is not entirely not secrete enzymes to
hormones): Bind to Monitoring: Focusing on clear. digest steroid and thyroid
plasma proteins in blood Carrier-bound hormones the free hormone pool hormones, allowing them
(reversible binding). are in dynamic equilibrium provides a more accurate to be taken orally (e.g.,
with the free hormone measure of the hormone’s birth control pills).
pool, providing a reserve active status in the body.
to replace the active free
pool. Adjustment: Ensuring the Hydrophilic hormones,
right levels of free like insulin, are
hormones helps maintain administered via non-oral
proper endocrine function routes (e.g., daily
and physiological balance. injections).
Hormonal Mechanism of Action
1. General Mechanism:
o Hormones induce effects by altering intracellular proteins.
o Induction of Effect: Hormone binds to a specific receptor on the target cell.
o The interaction between the hormone and the target cell produces a characteristic response,
which varies between different hormones and target cells, but not the signalling mechanism.
2. Receptor Location and Binding Mechanism:
o The location of receptors and the binding mechanism depend on the hormone’s solubility
(refer to image on the right).

o Hydrophilic Hormones:
▪ Function via second-messenger pathways (e.g., cAMP or Ca²⁺).
▪ Activation alters the activity of pre-existing intracellular proteins to produce an effect.
o Lipophilic Hormones:
▪ Function by activating specific genes in target cells.
▪ Induce the formation of new intracellular proteins to produce an effect.
Hormonal Mechanism of
Action:
Hydrophilic

• Hydrophilic hormones function via

2nd-messenger pathways (cAMP or
Ca2+)
• Activation alters activity pre-
existing intracellular proteins to
produce effect
Hormonal Mechanism of
Action:
Lipophilic

• Lipophilic hormones function by

activating specific genes in target
cells
• Induces formation of new
intracellular proteins to produce
effect
 Hormonal Mechanism of Action:
Gene Stimulation by Lipophilic
Hormones
1. Hormone Diffusion:
o Lipophilic hormone diffuses through the plasma membrane of the target cell.
2. Receptor Binding:
o Hormone binds to a specific receptor in the cytosol or nucleus, forming a hormone-receptor
complex.
3. Nuclear Translocation:
o The hormone-receptor complex translocates to the nucleus and binds to DNA at a specific
attachment site (Hormone Response Element, HRE).
4. Gene Activation:
o Binding of the complex to DNA activates specific genes within the target cell.
5. Transcription:
o The activated gene’s code is transcribed into mRNA.
6. mRNA Transport:
o mRNA leaves the nucleus and enters the cytoplasm, where it binds to ribosomes.
7. Protein Synthesis:
o mRNA directs the synthesis of specific proteins according to the DNA code in the activated genes.
8. Protein Processing:
o Newly synthesized proteins leave the ribosome and are processed into their proper conformation.
9. Cellular Response:
o The new protein produces the target cell’s ultimate response to the hormone.
Signal Amplification of
secondary messenger
pathway

[Link] of Pathway:
o Cells use a complicated system to
accomplish responses through
second-messenger pathways.
[Link] Effect:
o The pathway’s cascading
(multiplying) effect amplifies the
signal.
o Amplification: The output of the
system is greater than the input.
Apoptosis
1. Activation of Second Messengers:
o Universal in signal transduction pathways to ensure proper function, growth, survival, and reproduction.
2. Built-in Pathway for Cell Death:
o What?: Apoptosis is programmed cell death, also known as “cellular suicide.”
o Roles/Functions:
▪ Maintains balance of cell multiplication.
▪ Removes damaged or unnecessary cells.
▪ Prevents unregulated cell growth (e.g., tumours).
o Control:
▪ Mediated by caspases (enzymes) that cleave specific proteins to initiate cell death.
▪ Triggered by internal signals or external stimuli (e.g., hypoxia, immune reactions).
3. Comparison to Necrosis:
o Apoptosis:
▪ Controlled, orderly process.
▪ Does not cause inflammation.
▪ Cells shrink and form apoptotic bodies.
o Necrosis:
▪ Uncontrolled, often due to injury or infection.
▪ Causes inflammation and tissue damage.
▪ Cells swell and burst, releasing contents into the extracellular space.
Hormonal Mechanism of Action

[Link] Regulation:
o Membrane Receptors: Serve as links between extracellular first messengers
and intracellular second messengers.
o Regulation: Receptor number and affinity can be altered depending on
circumstances.
o Example: Chronic elevation of insulin in blood decreases insulin receptors.
Diseases Linked to
Receptor Malfunction:
Cause:
• Defective Growth Hormone Receptors: The
body produces normal levels of growth
hormone, but the receptors that should
respond to this hormone are defective.
Result:
• Abnormally Short Stature: Despite having
normal growth hormone levels, individuals
with Laron Dwarfism have short stature
because their bodies cannot utilize the
hormone effectively.
Contrast with Usual Dwarfism:
• Usual Dwarfism: Typically caused by a
deficiency in growth hormone production,
leading to short stature due to insufficient
hormone levels.
Diseases Linked to Receptor Malfunction:
• Whooping Cough:
• Caused by pertussis toxin, which prevents inhibition of adenyl
cyclase.
• Leads to a continuously active second-messenger pathway,
specifically increasing cyclic AMP (cAMP) levels within cells.
• Increased cAMP: Leads to dysregulation of cellular functions,
particularly in the respiratory tract.
• Mucus Production: Excessive cAMP causes increased mucus
secretion, contributing to the characteristic severe coughing fits.
• Immune Response: Impairs the immune system’s ability to
respond effectively, prolonging the infection.
• Airway Sensitivity: Heightened sensitivity and inflammation of the
airways, leading to the persistent and intense coughing spells
typical of whooping cough.
Diseases Linked to Receptor Malfunction:
• Cholera:
• Caused by a toxin that prevents G protein from converting GTP
to GDP.
• Ensures a continuously active G protein.
• Result: This persistent activation of the G protein stimulates
adenylate cyclase, increasing cyclic AMP (cAMP) levels.
• Physiological Consequences:
• Increased cAMP: Leads to excessive secretion of chloride ions
into the intestinal lumen.
• Water Loss: The high chloride ion concentration draws water into
the intestines, causing severe diarrhoea.
• Dehydration: Rapid fluid loss can lead to dehydration and
electrolyte imbalances, which are the primary dangers of cholera
Multiple effects of
Hormones

• Multiple Effects of Hormones

1. Different Effects on Target Cells:
o The same hormone can have different
effects on target cells due to:
▪ Different receptors for the
hormone.
▪ Different signal transduction
pathways.
▪ Different proteins for carrying
out the response.
Species-Specific Effects:

o Example: Thyroxine in Tadpoles

▪ Thyroxine, produced by the thyroid
gland, plays a crucial role in the
metamorphosis of tadpoles into frogs.
▪ It triggers the transformation by
promoting the development of limbs,
resorption of the tail, and other
changes necessary for the transition
from an aquatic to a terrestrial life
Cross-talk in cellular
signalling

• Cross-talk in cellular signalling refers to the

interactions between different signal transduction
pathways. This allows cells to integrate and respond
to multiple signals simultaneously, ensuring a
coordinated response.

• The image provided illustrates this concept well. It

shows how various components like G protein-
coupled receptors, second messengers (such as
cAMP), and enzymes (like adenylyl cyclase) interact.
These interactions can activate or inhibit different
pathways, leading to a final cellular response.
Essentially, cross-talk ensures that cells can
process complex information and react
appropriately to their environment.
 Non-hormonal signalling

Local Regulators: Gases:

Cytokines & Growth Factors: Nitric Oxide (NO):

• Examples: TNF-α, ILs, IGF • Produced from L-Arginine + O₂ by nitric oxide synthase
• Half-life: 2-30 seconds
• Activates guanylyl cyclase → cGMP
• Functions: Neurotransmitter, neuromodulator,
vasodilation
• Produced by endothelial cells, diffuses to smooth
muscle cells

Carbon Monoxide (CO):

• Activates guanylyl cyclase → cGMP
• Targets: Smooth muscle, neural tissue
Non-hormonal signalling
• Lipids: Prostaglandins (PGs):
• Characteristics:
• Locally acting chemical messengers
• Derived from arachidonic acid (20-C FA with 5-C ring)
• Produced by all tissues, inactivated locally before reaching blood
• Groups:
• PGA, PGE, PGF (based on 5-C ring structure)
• Identified by double bonds on side chains
• Types:
• Prostaglandins
Arachidonic acid
• Prostacyclins derivatives Eicosanoids
• Thromboxanes
• Leukotrienes
• Functions:
• Inflammation, platelet aggregation
• Different structures → different biological actions
• Same PG can have opposite effects in different tissues
Prostaglandin formation
Phospholipid Bilayer:
• Source of Arachidonic Acid.
Arachidonic Acid:
• Released by Phospholipase (PLA).
Pathways:
1. Leukotrienes:
1. Enzyme: Lipoxygenase (LOX)
2. Role: Inflammatory responses.
2. Prostaglandins:
1. Enzyme: Cyclooxygenase (COX)
2. Role: Inflammation, pain, fever regulation.
3. Thromboxanes:
1. Enzyme: Cyclooxygenase (COX)
2. Role: Platelet aggregation, blood clotting.
Key Points:
• Arachidonic Acid is central to producing eicosanoids.
• Different enzymes lead to different products with distinct biological roles.
• Understanding these pathways is crucial for pharmacology, especially anti-inflammatory
drugs.
 Prostaglandin formation elaborated
drawing
1. Starting Point:
• Phospholipid Bilayer: The cell membrane where Arachidonic Acid is stored.
2. Release of Arachidonic Acid:
• Enzyme: Phospholipase A2 (PLA₂) releases Arachidonic Acid from the membrane.
3. Pathways from Arachidonic Acid:
• Leukotrienes Pathway:
• Enzyme: Lipoxygenase (LOX)
• Products: Leukotrienes
• Role: Involved in inflammation.
• Prostaglandins Pathway:
• Enzyme: Cyclooxygenase (COX)
• Products: Prostaglandins
• Role: Regulate inflammation, pain, and fever.
• Thromboxanes Pathway:
• Enzyme: Cyclooxygenase (COX)
• Products: Thromboxanes
• Role: Help with blood clotting and platelet aggregation.

Key Points:
• Arachidonic Acid is a crucial molecule that can be converted into different signalling molecules.
• Enzymes like LOX and COX determine which pathway and products are formed.
• These products (Leukotrienes, Prostaglandins, Thromboxanes) have important roles in the body’s response to injury
and inflammation.