Ch. 6: Communication,

Integration & Homeostasis

Describe cell to cell communication

Explain signal transduction and signal

pathways

Review homeostasis and its control

pathways

Goals

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 = ?

Gap Junctions for Direct

Signal Transfer

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

Local Communication viaParacrines 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 Pathways

Signal molecule

(ligand)

Receptor

Intracellular signal

Target protein

Response

3 Receptor Locations

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.Fig 6-4

Membrane Receptor Classes

1. Chemically (ligand) gated channels

e.g.: nicotinic Ach receptor

2. Receptor enzymes

3. G-protein-coupledSignal 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 (2nd

messenger) protein kinase activation

Activated G-protein Opens Ion Channel

Muscarinic ACh receptor

Activated G-protein Alters IC Enzyme Activity

Compare to Fig 6-11

Epinephrine

Signal

Transduction

Novel Signal Molecules: Ca2+

Important IC signal

Can enter cell via voltage, ligand, and

mechanically gated channels

Also intracellular storage

Ca2+ 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, yetReceptors 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

3. Many systems have antagonistic controls (insulin/glucagon)

4. Chemical signals can have different effects on different tissues

Failure of homeostasis?

Fig 6-20

Maintenance 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

Receptors (or Sensors)

Different meanings for “receptor”: sensory vs. membrane receptors

Can be peripheral or central

Constantly monitor environment

Have threshold (= minimum stimulus necessary to initiate signal)

Fig 6-24

Afferent Pathway

From receptor to integrating

center

Afferent pathways of nervous

system: ?

Endocrine system has no afferent

pathway (stimulus comes

directly into endocrine cell)

Integrating Center

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

Efferent Pathway

From integrating center to

effector

NS electrical and chemical

signals

ES chemical signals

(hormones)

Effectors

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 organismallevel

◦ 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

2 types of feedback loops:- feedback loops

+ feedback loops Fig 6-27

Fig 6-26

The Body’s 2 Control Systems

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