Intercellular Communication

Cell and Molecular Physiology

 Overview
• The evolution of multicellular organisms led to
the development of mechanisms to tightly
coordinate the activities among cells
• From the knowledge we gather in cellular and
molecular physiology we learn that all cells
receive and process information
• External signals such as odorants ,chemicals, ions,
hormones, growth factors and neurotransmitters
can all serve as chemical messengers
 Overview
• It is also possible for other external signals
that are not considered chemical in nature
(e.g light and mechanical or thermal stimuli)
to be transduced into a chemical messenger
• Most chemical messengers interact with
specific cell surface receptors and trigger a
cascade of secondary events
 Overview
• However some hydrophobic messengers such
as steroid hormones and vitamins can diffuse
across the plasma membrane and interact
with cytosolic or nuclear receptors
Mechanisms of cellular communication

• Its now established cells communicate with

one another via chemical messengers.
• Within a given tissue, some messengers move
from cell to cell via gap junctions without
entering the ECF.
• In addition, cells are affected by chemical
messengers secreted into the ECF, or by direct
cell–cell contacts.
 Cont’d
• Chemical messengers typically bind to protein
receptors on the surface of the cell or, in some
instances, in the cytoplasm or the nucleus,
triggering sequences of intracellular changes
that produce their physiologic effects.
 Cont’d
• There are four general types of intercellular
communication mediated by messengers in the ECF:
• (1) Neural communication-Neurotransmitters are
released at synaptic junctions from nerve cells and
act across a narrow synaptic cleft on a postsynaptic
cell
• (2) Endocrine communication -in which hormones
and growth factors reach cells via the circulating
blood or the lymph
 Cont’d
• (3) Paracrine communication- In which the
products of cells diffuse in the ECF to affect
neighboring cells that may be some distance
away.
• 4) Autocrine communication -cells secrete
chemical messengers that in some situations
bind to receptors on the same cell, that is, the
cell that secreted the messenger
 Cont’d
• 5) Juxtacrine communication
• Some cells express multiple repeats of growth
factors such as transforming growth factor
alpha (TGFα) extracellularly on transmembrane
proteins that provide an anchor to the cell.
• Other cells have TGFα receptors.
• So TGFα anchored to a cell can bind to a TGFα
receptor on another cell, linking the two.
 Extracellular signaling molecules
• Four types of chemicals can serve as extracellular
signaling molecules
• -Amines i. e Epinephrine
• -Peptides and Proteins i.e Angiotensin II and insulin
• -Steriods- i.e Aldosterone, estrogens and retinoic
acid
• -Other small molecules i.e amino acids, nucleotides,
ions ( e.g Ca++),gases ( nitric oxide) lipids, purine
nucleotides and pyrimidine nucleotides
 Cont’d
• It is important to note that various parts of the
body, the same chemical messenger can
function as a neurotransmitter, a paracrine
mediator, a hormone secreted by neurons
into the blood (neural hormone), and a
hormone secreted by gland cells into the
blood
 Receptors for chemical messengers
• For a molecule to act as a signal it must bind to
a receptor
• Therefore a receptor is a protein ( in some
cases a lipoprotein ) on the cell surface or
within the cell that specifically binds to a signal
molecule ( the ligand).
• In some cases the receptor is itself an ion
channel and ligand binding produces a change
in Vm
 Cont’d
• In other cases the interaction of the ligand
with one or more receptors leads to an
association of the receptor with an effector
molecule that initiates cellular response.
• These effectors include enzyme channels,
transport proteins , contractile elements and
transcription factors
 Cont’d
• Receptors are not static components of the
cell
• Instead their numbers increase and decrease
in response to various stimuli, and their
properties change with changes in
physiological conditions
 Regulation of receptors
• For example
• Down regulation -When a hormone or
neurotransmitter is present in excess, the
number of active receptors generally
decreases
• Up regulation- in the presence of a deficiency
of the chemical messenger, there is an
increase in the number of active receptors
 Cont’d
• Two methods of down regulating
• Internalization- receptor mediated
endocytosis
• Desensitization-receptors chemically modified
making them less responsisve
 Classification of receptors
• Receptors can be divided into four categories
based on their associated mechanisms of
signal transduction
• 1) Ligand gated ion channels-These form
integral membrane proteins . Largely involved
in signaling between electrically excitable cells
• Also known as ionotropic receptors
 Cont’d
• 2) G-protein coupled receptors- Integral
plasma membrane proteins too. These work
indirectly through an intermedaiary- activate
or inactivate a separate membrane associated
enzyme or channel
• This intermediary is a heterotrimeric
guanosine triphosphate GTP-binding complex
called a G protein
 Cont’d
• Form the largest family of receptors on the cell
surface with more than 1000 members
• With a wide chemical diversity of their ligands
 Cont’d
• 3) Catalytic receptors- When activated by a ligand these
integral membrane proteins are either enzymes
themselves or part of an enzymatic complex
• E.g Receptor guanylyl cyclases- catalyses the generation
of cGMP from GTP
• Tyrosine kinase-associated receptors
• 4) Nuclear receptors- These are proteins located in the
cytosol or nucleus
• Are ligand-activated transcription factors
• These link extracellular signals to gene transcription
 Cont’d
• For example important signaling molecules
produce their effect not by binding to
receptors on the cell surface but by binding to
nuclear receptors
• i.e steroids and thyroid hormones bind to
receptors on the nucleus or in the cytoplasm
 Cont’d
• Therefore we can say that chemical
messengers act by
• (1) ion channel activation, (2) G-protein
activation, (3) activation of enzyme activity
within the cell, or (4) direct activation of
transcription.
source. Ganong (23rd edition)
 Mechanisms by which messengers act

• 1) Ligands such as acetylcholine bind directly

to ion channels in the cell membrane,
changing their conductance.
• 2) Thyroid and steroid hormones, 1,25-
dihydroxycholecalciferol, and retinoids enter
cells and act on one or another cytoplasmic or
nuclear receptors.
 Cont’d
• 3) Many other ligands in the ECF bind to
receptors on the surface of cells and trigger
therelease of intracellular mediators such as
cAMP, that initiate changes in cell function
 Cont’d
• The extracellular ligands are called first
messengers
• The intracellular mediators are called “second
messengers
 Second Messengers
• Second messengers are molecules that undergo a rapid
concentration changes in the cell following primary
messenger recognition.
• Some common second messenger molecules include :
• -Ca2+
• Ca2+ regulates a very large number of physiological
processes that are as diverse as proliferation, neural
signaling, learning, contraction, secretion, and fertilization,
• This means regulation of intracellular Ca2+ is of great
importance.
 Cont’d
• Cyclic adenosine monophosphate (cAMP)
• -Cyclic guanine monophosphate (cGMP)
• -Inositol trisphosphate (IP3)
• -Nitric oxide (NO).
 Cells can also communicate directly

• Through
• - Gap junctions
• -Tight junction
• -Membrane associated ligands