KIN 270 Michael Gaetz Ph.D.

Chapter 6: Communication, Integration, and Homeostasis

What we will review:

• • Cell-to-cell communication
• • Signal pathways
• • Novel signal molecules
• • Modulation of signal pathways
• • Homeostatic reflex pathways

Cell-to-Cell Communication: Overview

• • Physiological signals:
• • Electrical signals
• • Changes in the membrane potential of a cell
• • Chemical signals
• • Molecules secreted by cells into extracellular fluid (ECF)
• • Responsible for most communication within the body
• • Target cells respond to both signals.

Cell-to-Cell Communication: Local vs. long distance

• • Local communication includes:
• • Gap junctions
• • Contact-dependent signals
• • Local diffusion of signaling molecules to proximal cells

Long Distance Communication

• • Chemical signals released by the endocrine system are called hormones
• • Chemical signals released by nerve cells are called neurocrines.
• • Neurocrines that diffuse across a synapse are called neurotransmitters
• • Neurocrines that diffuse by paracrine signalling are called neuromodulators
• • Neurocrines that diffuse into the vascular system are called neurohormones.

Cytokines
• • All nucleated cells synthesize and secrete cytokines in response to stimuli
• • Cytokines control cell development and differentiation as well as the immune
response
• • Cytokines differ from hormones because they are not produced and stored by
endocrine tissue.

Signaling Pathways

• • Why do some cells respond to a chemical signal while others do not?

Signaling Pathways:

• • Why do some cells respond to a chemical signal while others do not?

• • A: Cells that respond have receptor proteins or “receptors” to which a
chemical signal or “ligand” binds.

Signaling Pathways:
• • Where a ligand binds usually depends on whether it is lipophilic or lipophobic
• • Lipophilic ligands are able to diffuse through the phospholipid bilayer of the
cell wall
• • Once inside the cell, they bind to receptors on structures in the cytosol or on
the nucleus (e.g. sex hormones)
• • Lipophobic ligands cannot diffuse through the phospholipid bilayer and
instead bind to receptors built into the cell wall.

Signaling Pathways:
• • There are 4 categories of receptor and pathways for lipophobic ligands. We
will cover 3 (skip integrin receptors):
• • Receptor (ion) channels
• • Receptor-enzyme
• • G protein-coupled receptors

Receptor Channels
• • The simplest structures with receptors are ligand-gated ion channels
• • Most are neurotransmitter receptors on nerve and muscle
• • When an extracellular ligand binds to a receptor, a membrane channel opens
that allows specific ion(s) to enter or exit the cell.

Receptor-enzymes
• • Receptor-enzymes have an extracellular receptor region and an
intracellular enzyme producing region
• • The enzyme region can be a part of the same protein as the receptor
or a separate protein
• • The enzymes are either protein kinases or guanylyl cyclase
• • Ligands include insulin, cytokines, and growth factors.

G protein-coupled receptors (GPCRs)

• • GPCRs have a complex receptor that links to a 3-part membrane G
protein
• • G proteins get their name from binding guanosine nucleotides
• • Inactive G proteins bind guanosine diphosphate (GDP)
• • When activated GDP is replaced by guanosine triphosphate (GTP)
• • G Protein animation

Adenylyl cyclase cyclic-adenosine monophosphate (c-AMP) pathway

• • Signal molecule binds to G protein–coupled receptor (GPCR), which activates
the G protein via GTP displacing GDP at the alpha subunit
• • The alpha subunit activates adenylyl cyclase, an amplifier enzyme
• • Adenylyl cyclase converts ATP to cyclic AMP
• • c-AMP activates protein kinase A
• • Protein kinase A phosphorylates other proteins, leading ultimately to a
cellular response

Ca2+ is an important intracellular signal

• • Ca2+ ions are responsible for several different types of interactions within
cells
• • At the conclusion of this course, you should be able to name several including
but not limited to:
• • Binding to calmodulin to alter enzyme and/or transporter activity
• • Binding to regulatory proteins such as troponin in skeletal muscle
• • Binding to secretory vesicles that contain neurochemicals
• • Binding to ion channels to alter their gating state
• • Entry into a fertilized egg results in embryo growth.

Gases Are Ephemeral Signal Molecules

• • Nitric oxide (NO)
• • A short acting paracrine and autocrine signaling molecule produced by
endothelial cells
• • NO (and citrulline) are produced by the enzyme nitric oxide synthase
that acts on arginine in the presence of O2
• • NO diffuses into smooth muscle and causes vasodilation
• • NO activates guanylyl cyclase second messenger systems and can act
as a neuromodulator and neurotransmitter.

Gases Are Ephemeral Signal Molecules

• • Carbon monoxide (CO)
• • Also activates guanylyl cyclase and cGMP
• • Targets smooth muscle and neural tissue
• • Hydrogen sulfide (H2S)
• • Targets cardiovascular system to relax blood vessels
• • Garlic is major dietary source of precursors

Some Lipids Are Important Paracrine Signals

• • When mapping the human genome, scientists realized that some receptors
were not linked to a signaling molecule
• • By working backwards, they realized that eicosanoid signal molecules
(derived from arachidonic acid) can be converted into different paracrine
signaling molecules
• • Membrane lipids are converted to arachidonic acid by the enzyme PLA2
(phospholipase A2)

Some Lipids Are Important Paracrine Signals

• • Leukotrienes are molecules produced by the combination of arachidonic acid
and the enzyme lipoxygenase
• • Leukotrienes are secreted by some white blood cells and play a role in
asthma and anaphylaxis
• • Prostanoids are produced by the enzyme cyclooxygenase (e.g. COX1 & COX2)
when acting on arachidonic acid and include Prostaglandins and
 Thromboxanes.
Some Lipids Are Important Paracrine Signals
• • Prostanoids act on many bodily tissues and affect sleep, inflammation, pain,
fever
• • Nonsteroidal anti-inflammatory drugs (NSAIDs) help prevent
inflammation by inhibiting COX enzymes
• • In addition to eicosanoids, Sphingolipids help regulate inflammation, cell
adhesion and migration, and cell growth and death.

One ligand may have multiple receptors

• • Q: How can one chemical have multiple effects on various targets?

One ligand may have multiple receptors

• • A: It’s not the ligand, it’s the receptor that receives the ligand that causes
specific action on the cell
• • Epinephrine is a good example:
• • It can have excitatory effects when binding to certain α receptors on smooth
muscle in the gastrointestinal (GI) tract causing blood vessel constriction
• • It can have inhibitory effects when binding to β receptors on smooth muscle
cells in the walls of blood vessels in skeletal muscle.

Receptor Saturation, Specificity, and Competition

• • Certain receptors can bind more than one ligand, but they have preference
(or an affinity) for one over the other (e.g. β2 receptors will be activated more
by epinephrine than norepinephrine
• • Ligands can also be either agonists or antagonists
• • Agonists activate a receptor, antagonists block them.

Up and Down Regulation of Receptors

• • A single cell has between 500 and 100,000 receptors on the cell membrane
alone
• • Receptor numbers and sensitivity are in a constant state of change
• • Receptors can be down-regulated by endocytosis or by desensitization
• • Up-regulation of receptors is when more receptors are added to a cell
membrane

Control Systems: Cannon’s Postulates

• • Walter Cannon is considered a pioneer in the field of physiology and
homeostasis
• • He developed 4 postulates related to health, homeostasis, and disease
states:
• • 1. The nervous system regulates the “fitness” of the internal environment
• • The nervous system coordinates and integrates all types of information in the
body to allow for optimal function given a specific set of conditions.

Control Systems: Cannon’s Postulates

• • 2. Some bodily systems are under tonic control
• “The radio is always on, but the volume can be turned up or down”
• An example of this would be parasympathetic regulation of vessel
diameter and heart rate.

Control Systems: Cannon’s Postulates

• • 3. Some bodily systems are under antagonistic control
• • A specific system, or part of a system, can be under the control of
antagonistic or opposing neural or hormonal inputs
• • e.g. Dynamic antagonism of the heart by sympathetic and parasympathetic
divisions of the autonomic nervous system
• • e.g. Hormonal: insulin vs. glucagon.

Control Systems: Cannon’s Postulates

• • 4. One chemical signal can have different effects in different tissues
• • Can you provide an example?
• • You should eventually be able to come up with a couple of solid examples.

Long-distance pathways maintain homeostasis

• • Long distance pathways can involve neural, hormonal, or cytokine signaling
to regulate the functioning of distant tissue
• • Response loops have 3 primary components: input, integration, and output
• • There are 7 steps for a simple neural reflex:
• • 1. Stimulus – a change in a physical variable
• • Examples?

Long-distance pathways maintain homeostasis

• • 2. Sensor or receptor
• • Sensory receptors detect change in a physical stimulus
• • There are receptors that are functionally linked to the central nervous
system (CNS)
• • Peripheral receptors are located outside of the CNS
• • All sensors have a “threshold” or a minimum amount of stimulation
that will allow them to be activated.

Long-distance pathways maintain homeostasis

• • 3. Input signal “pathway”
• • Does the stimulus act directly on the integrating centre cells or does it
travel via sensory receptors and nerve cells?

Long-distance pathways maintain homeostasis

• • 4. Integration Centre (central nervous system)
• • The integrating centre in a reflex pathway contains the cells that
receive information about a stimulus and can initiate an appropriate
response or adjustment
• • If the stimulus information comes from a single source, this is
relatively straightforward
• • If complex or competing information is being received, integration
 necessarily becomes more complex.
Long-distance pathways maintain homeostasis
• • 5. Output signaling
• • This varies depending on whether output is neural, hormonal, or cytokine
based
• • Neural outputs require a nerve cell to be activated and to transmit
information to a target (effector)
• • Hormonal and cytokine-based information travels through fluid systems –
primarily the vascular system.

Long-distance pathways maintain homeostasis

• • 6. Targets
• • Targets are referred to as effectors.
• • They are any cells/tissue in the body that have the appropriate receptors and
change their functioning in the presence of specific output signals.

Long-distance pathways maintain homeostasis

• • 7. Responses
• • There is a response at the cellular level that dictates the response of the
effector system in general
• • Examples?