Ch' 6: Communication, Integration

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Ch. 6 Communication, Integration Homeostasis
Goals

• Describe cell to cell communication
• Electrical or Chemical only
• Explain signal transduction
• Review homeostasis

N.B. Running Problem, Diabetes Mellitus
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Cell to Cell Communication

• 75 trillion cells (In Scientific Notation??)
• 4 basic methods of cell to cell communication (p
  175)
• Direct cytoplasmic transfer (Gap Junctions)
• Contact dependant signals (Surface Molecules)
• Short distance (local diffusion)
• Long distance (through either chemical or
  electrical signals)
• Cell receiving signal ? receptors

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1. Gap Junctions for Direct Signal Transfer

• Connexins from each cell form connexon (channel)
• Gate open ? cytoplasmic bridges form functional
  syncytium
• Transfer of electrical and chemical signals
  (ubiquitous, but particularly in heart muscle and
  smooth muscle of GI tract)

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2. Contact-Dependent Signals

• Require cell-cell contact
• Surface molecules bind
• CAMs Cell Adhesion Molecules
• Bidirectional Communication Possible

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3. Short distance (local diffusion)

• Paracrines and Autocrines (Chemical signals
  secreted by cells)
• Para- next to
• Auto- self
• Mode of transport - diffusion (slow)
• Histamine, cytokines, eicosanoids
• Many act as both

Autocrine
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4. Long Distance Communication

• Body has two control systems
• Endocrine system communicates via hormones
• Secreted where? Transported where and how?
• Only react with ____________
• Nervous system uses electrical (along the axon)
  and chemical (at the synapse) signals (APs vs.
  neurotransmitters and neurohormones)

Fig 6-2
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Long Distance Communication
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Cytokines for Local and Long Distance Signaling

• Act as paracrines, autocrines or hormones
• Comparison to hormones (sometimes blurry)
• Broader target range
• Made upon demand (like steroids, no storage in
  specialized glands)
• Involved in cell development and immune response
• Terminology A zoo of factors in a jungle of
  interactions surrounded by deep morasses of
  acronyms and bleak deserts of synonyms

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Signal Pathways

• Signal molecule (ligand)
• Receptor
• Intracellular signal
• Target protein
• Response

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Three Receptor Locations
Membrane, Cytosolic or Nuclear

• Lipophilic ligand
• enters cell and/or nucleus
• Often activates gene
• Slower response
• Lipophobic ligand
• can't enter cell
• Membrane receptor
• Fast response

Fig 6-4
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Membrane Receptor Classes

• Ligand - gated channel
• Receptor enzymes
• G-protein-coupled
• Integrin

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Direct Mechanisms via Ligand-gated Channel
Nicotinic ACh receptor
Change in ion permeability changes membrane
potential
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Signal Transduction

• Activated receptor alters intracellular molecules
  to create response
• First messenger ? transducer ? amplifier ? second
  messenger

Fig 6-8
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Most Signal Transduction uses G-Protein
G-Protein is a membrane-associated protein that
binds to GDP

• Hundreds of types known
• Bind GDP / GTP (name!)
• Activated G proteins
• Open ion channels
• Alter intracellular enzyme activity, e.g. via
  adenyl cyclase (amplifier) ? cAMP (2nd messenger)
  ? protein kinase activation ? phosphorylated
  protein

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G - Protein mediated Signal Transduction
Muscarinic ACh receptor
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Epinephrine Signal Transduction
Compare to fig 6-11
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Other signal Molecules

• Not all are proteins
• Ca2 is a common cytosolic messenger
• NO (nitric oxide) is a neurotransmitter
• Lipids
• Leukotrienes cause contraction of bronchiolar
  smooth muscle
• Prostanoids have several communicative roles,
  e.g., inflammation

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Modulation of Signal Pathways

• Receptors exhibit
• Saturation, yetReceptors can be up- or
  down-regulated (e.g. drug tolerance)
• Specificity, yet- Multiple ligands for one
  receptor Agonists (e.g. nicotine) vs.
  antagonists (e.g. tamoxifen)
• - Multiple receptors for one ligand (see Fig
  6-18)
• Competition
• Aberrations in signal transduction causes many
  diseases (table 6-3)
• Many drugs target signal transduction pathway
  (SERMs, ?-blockers etc.)

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In Summary Receptors Explain Why

• Chemicals traveling in bloodstream act only on
  specific tissues
• One chemical can have different effects in
  different tissues

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Signal molecule receptors exhibit

• Specificity
• Competition
• Saturation
• B and C only
• A, B, and C

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Ligand receptor specificity is so precise that

• Each receptor will bind only one ligand
• Each ligand will bind to only one type of
  receptor
• One can reliably predict the response of a target
  knowing the identity of the ligand
• A, B, and C
• None of the above

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The intracellular effector in chemical signaling
is often

• a hormone
• protein kinase
• ATP
• a membrane receptor molecule
• cholesterol

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Homeostasis and Homeodynamics

• Cannon's Postulates (concepts) of properties of
  homeostatic control systems
• Nervous regulation of internal environment
• Tonic level of activity
• Antagonistic controls (insulin/glucagon)
• Chemical signals can have different effects on
  different tissues
• Failure of homeostasis?

Fig 6-19
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Tonic Control
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Control Pathways Response and Feedback Loops

• Maintain homeostasis
• Local paracrines and autocrines
• Long-distance - reflex control
• Nervous
• Endocrine
• Cytokines

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Steps of ReflexControl
Stimulus Sensory receptor Afferent
path Integration center Efferent path Effector
(target cell/tissue) Response
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Receptors (or Sensors)

• Different meanings for receptor sensory
  receptor vs. membrane receptor
• Can be peripheral or central
• Constantly monitor environment
• Threshold ( minimum stimulus necessary to
  initiate signal)

Fig 6-23
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Afferent Pathway

• From receptor to integrating center
• Afferent pathways of nervous system ?
• Endocrine system has no afferent pathway
  (stimulus comes directly into endocrine cell)

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Integrating Center

• Neural reflexes usually in the CNS endocrine
  integration in the endocrine cell itself
• Receives info about change
• Interprets multiple inputs and compares them with
  set-point
• Determines appropriate response (? alternative
  name control center)

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Efferent Pathway

• From integrating center to effector
• NS ? electrical and chemical signals
• ES ? chemical signals (hormones)

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Effectors

• Cells or tissues carrying out response
• Target for NS
• muscles and glands and some adipose tissues
• Target for ES
• any cell with proper receptor

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In a feedback loop, effectors that bring about
change receive information from

• a stimulus
• the control center
• receptors
• a response mechanism

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Responses at 2 levels

• Cellular response of target cell
• opening of a channel
• Modification of an enzyme etc...
• Systemic response at organismal level
• vasodilation, vasoconstriction
• Lowering of blood pressure etc....

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Feedback Loops Modulate the Response Loop

• Response loop is only half of reflex! ?
  Response becomes part of stimulus and feeds back
  into system.
• Purpose keep system near a set point
• 2 types of feedback loops
• - feedback loops
• feedback loops

Fig 6-25
Fig 6-26
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Homeostasis Dynamic Equilibrium with
Oscillation around Set Point
Fig 6-15
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Negative and Positive Feedback
NOT homeostatic !!
Homeostatic
examples
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Negative Feedback Example
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Feedback Loop
fig 6-27
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Both insulin and glucagon are peptide hormones
that target liver cells. The response of the
target cells to each of these two hormones is
opposite. This information implies that

• the two hormones bind to different cell surface
  receptors.
• one hormone binds to a receptor on the cell
  membrane and the other to an intracellular
  receptor.
• each of the two hormones uses a different second
  messenger.
• both hormones interact with receptors at the cell
  nucleus.
• A and C

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Positive feedback loops in models assume that
secondary effects ________ the basic trend, while
negative feedback loops assume that secondary
effects tend to  _________ the basic trend.

• counteract reinforce
• reinforce counteract.
• self-limit retard.
• enhance promote.

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The Bodys 2 Control Systems

• Variation in speed, specificity and duration of
  action
• The two systems allow for 4 different types of
  biological reflexes
• Simple (pure) nervous
• Simple (pure) endocrine
• Neurohormone
• Neuroendocrine (different combos)

Fig 6-30
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NS ES are linked in a continuum
6 basic patterns
1
2
3
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Continuum continued . . . .
4
5
6
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Which of the following is not a method used in
maintaining homeostasis in the body?

• behavioral changes
• hormonal action
• negative feedback loops
• positive feedback loops
• All of the above are used to maintain homeostasis

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The act of breathing raises the blood oxygen
level, lowers the blood CO2 concentration, and
raises the blood pH. According to the principles
of negative feedback, sensors that regulate
breathing should respond to

• a rise in blood oxygen
• a rise in blood pH
• a rise in blood carbon dioxide concentration
• all of the above

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the end