Human Physiology: Unit-1
Intercellular Communication
BY
DR BOOMINATHAN Ph.D.
M.Sc.,(Med. Bio, JIPMER), M.Sc.,(FGSWI, Israel), Ph.D (NUS, SINGAPORE)
PONDICHERRY UNIVERSITY
V Lecture
14/August/2012
Source: Collected from different sources on the internet and modified by Dr Boominathan Ph.D.
Intercellular Commication
Intercellular Communication
• Cells of body must communicate with one another
• Coordinates organ systems
• Takes place directly:
– Physical contact between cells
• Gap junctions
• Direct linkage of surface markers
• Or indirectly
– Extracellular chemical messengers or
signal molecules
– Specific to target cell receptors
Chemical Messengers
• Four types of chemical messengers
– Paracrines
• Local chemical messengers
• Exert effect only on neighboring cells in immediate
environment of secretion site
– Neurotransmitters
• Short-range chemical messengers
• Diffuse across narrow space to act locally on
adjoining target cell (another neuron, a muscle, or a
gland)
General Schemes of Intercellular Signalling
Extracellular signaling
molecules released by
cells occurs over distances
from a few microns –
autocrine (c)
and paracrine (b)
signaling to
several meters in endocrine (a)
signaling.
In some instances,
receptor proteins attached to the
membrane of one cell interact
directly with receptors on an
adjacent cell (d).
© 2000 by W. H. Freeman and Company. All rights reserved.
Paracrine secretion
Neurotransmitter secretion
Chemical Messengers
– Hormones
• Long-range messengers
• Secreted into blood by endocrine glands in response
to appropriate signal
• Exert effect on target cells some distance away from
release site
– Neurohormones
• Hormones released into blood by neurosecretory
neurons
• Distributed through blood to distant target cells
Chemical Messengers
• Cell responses brought about primarily by signal
transduction
– Incoming signals conveyed to target cell’s interior
• Binding of extracellular messenger (first messenger)
to receptor brings about intracellular response by
either
– Opening or closing channels
• Chemically gated receptor channel
– Activating second-messenger systems
• Activated by first messenger
– Receptor-enzyme
• Relays message to intracellular proteins that carry out
dictated response
– G-protein coupled receptor
Receptor-enzyme:
Tyrosine kinase pathway
Hormones
• Endocrinology
– Study of homeostatic activities accomplished by
hormones
• Two distinct groups of hormones based on
their solubility properties
– Hydrophilic hormones
• Highly water soluble
• Low lipid solubility
– Lipophilic hormones
• High lipid solubility
• Poorly soluble in water
Mechanism of
hydrophilic
hormones via cyclic
AMP second
messenger pathway
Mechanism of action of hormones
Lipophilic hormones
Hydrophilic hormones
Comparison of Nervous System and Endocrine
System
Animation: Mechanism of action
of a peptide hormone
Animation: Mechanism of action
of a steroid hormone
Questions
1.
2.
3.
4.
5.
6.
7.
8.
9.
There are 3 ways cells communicate. The 2 direct means of
communication is through ___________ and _______________. Cells
indirectly communicate through _______________.
Name and describe the 4 types of chemical messengers. Include which
fluid medium they travel through: blood, extracellular fluid, intracellular
fluid.
Why is a neurotransmitter different than paracrine signalling?
What is a ligand? What is a receptor?
How does a chemical messenger “know” which organ to affect?
Name 3 ways that an extracellular chemical messenger can bring about an
intracellular response.
Is the response between a chemical messenger and a particular receptor
always the same?
How can a chemical receptor elicit a different response inside a cell?
In a second messenger system, where does the first messenger bind?
Where is the second messenger?
Questions
11. There are 2 major 2nd messengers: cyclic AMP and Ca2+ . Describe the
action of a hydrophilic hormone via activation of the cyclic AMP 2nd
messenger pathway. If you draw pictures, you must label everything and
explain what is happening.
12. How does using an 2nd messenger system amplify the response inside the
cell?
13. How do some chemical messengers affect gene activity (hence, protein
synthesis) within a cell?
14. Which type of hormone can affect gene activity, hydrophilic or lipophilic?
Why?
INTRACELLULAR SIGNAL TRANSDUCTION:
A Journey from the Plasma Membrane to the Nucleus
(with interesting stops along the way)
Thanks to
Paula Tracy, Ph.D.
paula.tracy@uvm.edu
INTRACELLULAR SIGNALING:
Signal Transduction
Cell membranes, as well as the cell cytoplasm and even the cell nucleus, contain cell-specific
receptors for various ligands, which are involved in outside-inside signaling,
i.e. signal transduction.
Ligands include hormones, growth factors, cytokines, prostaglandins and proteases.
Hormones are involved in a variety of metabolic processes that maintain homeostasis
e.g. fuel metabolism.
Particularly noteworthy in that regard are glucagon, insulin ,epinephrine
and norepinephrine.
Growth factors are involved in mitogenesis, whereas cytokines play critical roles in the
differentiation, proliferation and function of various cell lineages..
Interaction of such ligands with their membrane, cell-specific receptors or intracellular
receptors causes conformational changes in the receptor and, in many instances receptorassociated cytoplasmic proteins.
Such events result in the initiation of a cascade of importance, but as yet incompletely
understood, events leading to e.g. enzyme activation, differentiation and/or cell division.
General Schemes of Intercellular Signalling
Extracellular signaling
molecules released by
cells occurs over distances
from a few microns –
autocrine (c)
and paracrine (b)
signaling to
several meters in endocrine (a)
signaling.
In some instances,
receptor proteins attached to the
membrane of one cell interact
directly with receptors on an
adjacent cell (d).
© 2000 by W. H. Freeman and Company. All rights reserved.
FORCES DRIVING SELECTION OF CURRENT MECHANISMS
Need for coordinated intercellular communication
Need to translate extracellular signals into series of intracellular events,
while allowing for specificity
Specificity Determinants:
1. Specific receptors on or in the target cells recognize an appropriate ligand.
2. Specific response to receptor occupancy - effector pathways
Diversity of intercellular communication is achieved with hundreds of
signaling molecules, including...
Proteins, small peptides, amino acids, nucleotides, steroids,
fatty acid derivatives, and even dissolved gases such as NO and CO
Intracellular receptors:
Receptor Classes
- signaling molecules include
steroid hormones, retinoids,
thyroxine, etc
- receptor-hormone complex
acts a transcription factor
to alter transcription of certain
genes
Cell surface receptors:
- signaling molecules include
peptide hormones, ephineprines,
insulin, growth
factors, cytokines, etc
-binding, and subsequent events,
triggers an  or  in the
cytosolic concentration of
a second messenger; or the
activated,bound receptor acts
as a scaffold to recruit and
activate other intracellular
proteins
© 2000 by W. H. Freeman and Company. All rights reserved.
ADVANTAGES
1. Each cell is programmed to respond to specific combinations of signaling molecules.
2. Different cells can respond differently to the same chemical signal.
Molecular Biology of the Cell, 2002
HORMONES - First class of signaling molecules defined
Secreted from endocrine cells - specialized signaling cells that
control the behavior of an organism as a whole:
1. Differ from other intracellular mediators
2. Usually stimulate metabolic activities in tissues remote from the secretory organ
3. Active at very low concentrations (pM - M)
4. Response to hormonal signal comes as a direct and rapid result of its secretion
5. Metabolized rapidly so effects are, in most instances, short-lived, leading to
rapid adaptations to metabolic changes
Hormone types:
1. Peptides or polypeptides - insulin, glucagon, growth hormone, insulin-like
growth factors, vasopressin, prolactin….
2. Glycoproteins - follicle stimulating hormone (FSH), thyroid stimulating
hormone (TSH)…
3. Steroids - glucocorticoids (aldosterone, cortisol), steroids (progesterone,
testosterone), retinoic acid…
4. Amino acid derivatives - epinephrine, norepinephrine, thyroxine, triidothyronine
AGONISTS vs. ANTAGONISTS
Agonist
mimics a hormone in binding productively to a receptor
Antagonist
mimics a hormone stereochemically, but binds to the receptor
non-productively, inhibiting the action of the natural hormone
Agonist
e.g. important therapy
in asthma
Hormone
binds 2 receptor in lung 
bronchial relaxation
binds 2 receptor in heart muscle 
increased heart rate
Antagonist
control heart beat
RECEPTOR CHARACTERISTICS
1. Participates in transduction of the signal from the external messenger to
some component of the metabolic machinery
2. Has at least one additional functional site which is altered by ligand binding
(allosteric site)
3. Ligand binding to receptors is saturable, resembling Michaelis-Menten kinetics
© 2000 by W. H. Freeman and Company. All rights reserved.
4. Ligand-receptor interaction characterized by tight binding (Kd = pM - M)
Molecular Biology of the Cell, 2002
Simple Intracellular Signaling Induced by an Extracellular Signaling Molecule
A signaling molecule activates its receptor  activation of an intracellular signaling pathway, i.e. a series of signaling
proteins, which may interact with a target protein to change the behavior of the cell.
Glucagon
Epinephrine
Thrombin
Insulin
Growth factors
Molecular Biology of the Cell, 2002
THREE LARGEST CLASSES OF CELL SURFACE RECEPTORS