Ch. 6: Communication,
Integration & Homeostasis
Goals

Describe cell to cell communication

Explain signal transduction and signal pathways

Review homeostasis and its control pathways

Cell to Cell Communication
75 trillion cells / 2 types of signals
4 basic methods of cell to cell communication:
1.
Direct cytoplasmic transfer
2.
Contact dependent signals
(see IS discussion)
3.
Short distance (local)
4.
Long distance ( through combination of signals)
Cell receiving signal = ?


Connexins form connexons (channels)

Gate open  cytoplasmic bridges form functional syncytium

Transfer of electrical and chemical signals
(ions and small molecules)

Ubiquitous , but particularly in heart and GI tract muscle

Paracrines and Autocrines
(Chemical signals secreted by cells)
Mode of transport ?
Examples: Histamine, cytokines, eicosanoids
Many act as both

Long Distance Communication
Body has two control systems:
1) Endocrine system communicates via hormones
◦ Secreted where? Transported where and how?
◦ Only react with ____________
2) Nervous system uses electrical and chemical signals (APs vs. neurotransmitters and neurohormones)
Fig 6-2

Cytokines for Local and Long
Distance Signaling



Act as paracrines, autocrines or hormones
Difference to “real” hormones
(sometimes blurry → e.g. EPO):
◦ Broader target range
◦ Made upon demand (no storage in specialized glands)
Involved in cell development and immune response

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

Fig 6-4
Cytosolic or Nuclear
Lipophilic ligand enters cell.
Often activates gene.
Slower response.
Cell membrane
Lipophobic ligand cannot enter cell.
Outer surface receptor needed.
Faster response.

1.
2.
3.
Membrane Receptor Classes
Chemically (ligand) gated channels
e.g.: nicotinic Ach receptor
Receptor enzymes
G-protein-coupled
Signal transduction

Direct Mechanisms via Chemically Gated
Channel: Nicotinic ACh receptor
Change in ion permeability changes membrane potential

Signal
Transduction

Activated receptor alters intracellular molecules to create response

First messenger
 transducer  amplifier  second messenger
Fig 6-8

Most Signal Transduction uses G-Protein
100s of G protein-coupled receptor types known
G protein is membrane transducer (binds GDP /
GTP  name!)
Activated G proteins
1.
open ion channels , or
2.
alter intracellular enzyme activity , e.g.: via adenyl cyclase (amplifier)  cAMP (2 nd messenger)  protein kinase activation 

Activated G-protein Opens Ion Channel
Muscarinic ACh receptor

Activated G-protein Alters IC Enzyme Activity
Epinephrine
Signal
Transduction
Compare to
Fig 6-11

Ca 2+

Important IC signal

Can enter cell via voltage, ligand, and mechanically gated channels

Also intracellular storage

Ca 2+ signals lead to various types of events
→
Movement of contractile proteins
→
Exocytosis

Gases and Lipids as Signal Molecules

NO is made from arginine
◦ short acting auto- and paracrine
◦ in brain and in blood vessels

CO in nervous tissue and smooth muscle

Eicosanoids are arachidonic acid derivatives
◦ Leukotrienes (important in asthma)
◦ Prostanoids (ubiquitous) also important in inflammation etc.

Modulation of Signal Pathways
Receptors exhibit
Saturation , yet
Receptors can be up- or down-regulated (grow fewer, grow more)
Excess stimulation and 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  _____________ (table 6-3)
Many drugs target signal transduction (SERMs,  -blockers etc.)

In Summary:
Receptors Explain Why
Chemicals traveling in bloodstream act only on specific tissues
One chemical can have different effects in different tissues

Control Pathways: Response and
Feedback Loops
Cannon's Postulates (concepts) of properties of homeostatic control systems
1.
Nervous regulation of internal environment
2.
Tonic level of activity → “how much?”, not ON or
OFF regulated by nerve signal frequency
Fig 6-20
3.
Many systems have antagonistic controls
(insulin/glucagon)
4.
Chemical signals can have different effects on different tissues
Failure of homeostasis?

Via local or long distance pathways

Local: autocrines and paracrines

Long-distance: reflex control
◦ Nervous
◦ Endocrine
◦ both

Steps of Reflex Control
Stimulus
Sensory receptor
Afferent path
Integration center
Efferent path
Effector (target cell/tissue)
Response
Fig 6-23


Different meanings for “receptor”: sensory vs. membrane receptors

Can be peripheral or central

Constantly monitor environment
Fig 6-24

Have threshold (= minimum stimulus necessary to initiate signal)

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

Receives info about change
Interprets multiple inputs and compares them with set-point
Determines appropriate response
( → alternative name: control center)
Location depends on type of reflex





Cells or tissues carrying out response

Target for NS:
_________________________________

Target for ES:
__________________________________

Response Loops Begin with Stimulus –
End with Response
Response takes place at 2 levels
1.
Cellular response of target cell
◦ Opening of a channel
◦ Modification of an enzyme etc...
2.
Systemic response at organismal level
◦ Vasodilation, vasoconstriction
◦ Lowering of blood pressure etc....

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
Fig 6-26
2 types of feedback loops:
- feedback loops
+ feedback loops
Fig 6-27


Variation in speed, specificity and duration of action

Compare the different types of reflexes
(Table 6-5)
1.
Simple (pure) nervous
2.
Simple (pure) endocrine
3.
Neuro-hormone
4.
Neuro-endocrine (different combos)
Fig 6-31

Diabetes mellitus