Putting it all together:

Signals in animals
Part 1: Focusing on
epinephrine and leptin
1

Representing signal transduction

pathways
A
B
Inhibitor
C

Common enzyme-linked receptor

signaling pathway: activate Ras and Raf

Signal received

Autophosphorylation:

(RAF)

AMPLIFICATION at every step

Common enzyme-linked receptor

signaling pathway: activate Ras and Raf

Signal received

Autophosphorylation:
receptor
phosphorylates itself

this is not a G-protein

It is the ENZYME of the enzymelinked receptor

AMPLIFICATION at every step

Heres an example from literature

of a complex signaling pathway
Challenge: identify the
following components:
1. a G-protein coupled
receptor, and which
enzyme it activates
2. an enzyme-linked
receptor, and the
second messenger
pathway it activates
3. an inhibitor, and what
it inhibits.

Miyashiro K , Eberwine J. PNAS 2004;101:17329-17330

Students will apply general principles of biology,

specifically hormone signaling, to explain
homeostatic control of vasodilation and
vasoconstriction for stress responses.

Focus: epinephrine

Circulating hormones: small fluctuations lead to large responses

Different tissues, different receptors different responses

Epinephrine:

Circulating hormones: small

fluctuations create large responses
Normal circulating levels of hormones:
0.1 20 nmol/ L
A normal human contains
5-6 L of blood, and about 10 14 cells
That works out to very approximately
1-100 hormone molecules per cell.
The body is sensitive to even very small fluctuations in
hormone levelswhy?

8
8

Circulating hormones: small

fluctuations create large responses

Hormones: Brief signals, potent responses

There are two basic receptor subtypes
for epinephrine, alpha and beta.
This is the 1-receptor.
The signal is transduced as long as epinephrine
is present in the blood and bound to the
receptor
Epinephrine is broken down in the blood by
the enzyme Monoamine Oxidase (MAO).
This is the enzyme blocked by MAOIs
(a category of antidepressant).
Figure 49.18

10

Hormones: Brief signals, potent responses

Time (seconds after epinephrine exposure)

cAMP levels in heart muscle

cells increase immediately after
a pulse of epinephrine

Figure 49.17

11

Hormones: Brief signals, potent responses

Second messenger: ______

Downstream interactions:
Rapid response to cAMP:

Slower, more sustained

response to cAMP:

Figure 49.17

12

Phosphorylase catalyzes the production of glucose

from glycogen. What is glycogen?

A.
B.
C.
D.
E.

Just another name for starch

Glucose monomers linked together in a chain
A polypeptide
An enzyme of glycolysis
A fatty acid used for storing energy

figure 49.16

13

Hormones: Different tissues, different

responseswhy?
Tissues with the -1
adrenergic receptor :
Cardiac muscle

Response of cardiac muscles:

contract harder

Skeletal muscle arteries

Small coronary arteries

Response of smooth muscles in arteries

to epinephrine:
RELAX (Vasodilation)
Allow more blood flow

Liver

activate phosphorylase-pump more glucose into blood

Coordinated effect: Improve blood flow to heart and skeletal muscles to

prepare for physical activity
14

Hormones: Different tissues, different

responses
Tissues with the -1
adrenergic receptor :

But wait...

Skeletal muscle arteries

Small coronary arteries

Arteries in:
Skin
Gastrointestinal tract
Kidneys
Brain

Response of smooth muscles in

arteries to epinephrine:
RELAX (Dilation)
Allow more blood flow

Response of smooth muscles in

these arteries to epinephrine:
CONTRACT (Vasoconstriction)
Reduce blood flow to these areas
15

Hormones: Different tissues, different

responses
The other tissues have -1
receptors and also another
receptor subtype, -1.
-1 receptors are more sensitive
to epinephrine
but -1 receptors override the
effects of -1 receptor activation

Smooth muscle contraction

16

Hormones: Different tissues, different

responses

Diameter
of blood
vessels
serving
skin

Diameter
of blood
vessels
serving
heart

concentration of
epinephrine in blood

concentration of
epinephrine in blood

Systemic response:
Diversion of blood to inner organs, particularly heart and skeletal muscles.
Diversion of blood away from organs that are not essential for immediate
17
survival (skin, digestion, kidneys, brain)

Summary slide: response to epinephrine depends on

epinephrine levels, receptor types, and cell type
Red signal: epinephrine
-1 adrenergic receptor: GPCR PLC contraction
-1 adrenergic receptor: GPCR cAMP phosphorylase

pupil

Smooth muscle:
gut capillaries

Smooth muscle:
skeletal
capillaries

liver

Cardiac
muscle

Low levels of epinephrine: triggers -1 receptors

no response
relax: dilation
relax: dilation

phosphorylase

increase
contractions

High levels of epinephrine: triggers -1 receptors

contract
contract:
relax: more
(pupil dilation)
constriction
dilation

more
phosphorylase

more
contractions

Leptin signaling (p 1001-1003)

We will cover the experiment in detail during
recitations after break.
(posted ahead of time if youd like to try it)

19

You should be able to:

identify and give examples of the 5 categories of chemical signals in

animals (table 49.1), and categorize them as local or distance
signals

know which gland releases epinephrine (see 49.2)

Understand why structure of the signal affects where the receptor

for the signal will be (see figure 49.3), and predict where to find the
receptor if given the chemical structure of a signal

Explain why even small fluctuations in blood hormone levels can

have profound effects on cells (and also why not all cells respond to
any particular hormone)

20

You should be able to:

Answer application questions about the short-term

response to stress (fight or flight response) mediated by
the release of epinephrine, similar to the clicker questions
in this presentation

Answer application questions about leptin signaling (see

p 1001-1003, and also the recitation handout)

Anticipate what would happen if any component in either

signaling pathway were mutated or altered in some
fashion
21