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Chapter Twenty
Chemical Messengers:
Hormones, Neurotransmitters,
and Drugs
Goals
1. Describe the origins, pathways, and actions of hormones.
2. List identify and describe the different chemical types of
hormones.
3. To contrast the sequence of events in epinephrine’s action
as a hormone, with that of a hydrophobic hormone
4. Be able to describe origins, pathways, and actions of
neurotransmitters.
5. Be able to outline the events in acetylcholine’s action as a
neurotransmitter and give examples of its agonists and
antagonists
6. Be able to identify neurotransmitters and drugs active in
these conditions.
Two Systems For Messenger Molecules
Endocrine: 
hormone is
transported by the
circulatory system
 Neural: electrical
signal travels along
a neuron and
releases a
neurotransmitter
Distance Messages
Endocrine system
•Hormones, chemical
messengers that
circulate in the
bloodstream.
Local Messenger Molecules
The nervous system
• Faster means of
communication
• Neurotransmitters
emitted travel
between two neurons
or from a neuron to a
target cell.
– trigger electrical
impulses in nerve cells
Both Use Messenger Molecules &
Receptors
1. Hormones and
neurotransmitters
ultimately connect
with a target.
2. The receptor
causes a biochemical
response to occur
– The contraction of
a muscle
– The secretion of
another
biomolecule.
Major Endocrine Glands
1. Thyroid gland: Releases thyroxin, - an amino
acid derivative that influences energy use,
oxygen consumption, growth and development
2. Adrenal gland: Releases epinephrine and nor
epinephrin. Increase of heart rate, and release
of glucose from storage, and increase heart rate
3. Ovaries and Testes: Release testosterone,
estrogen, progesterone.
Development of secondary sexual characteristics, maturation
of sperm and eggs
4. Pituitary gland (found in the brain)
Adrenocorticotropic hormone, growth hormone,
follicle-stimulating hormone, luteinizing hormone,
vasopressin, thyrotropin
Hypothalmus Regulation
Section of the brain just above the
pituitary gland, regulates through
1. Direct neural control: A
nervous system message
initiates release of hormones by
the adrenal gland.
2. Direct release of hormones: Hormones move from
the hypothalamus to the posterior pituitary gland,
where they are stored until needed.
2. Indirect control through release of regulatory
hormones: Regulatory hormones from the
hypothalamus stimulate or inhibit the release of
hormones by the anterior pituitary gland, these
stimulate release of other hormones by target tissues.
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Chapter Twenty
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Three Types of Hormones
Amino Acid derivatives
Polypeptides
Steroids
Amino Acid Derivatives as Hormones
1. Most are hydrophilic because most amino acids
are polar
2. Unlike most amino acids, thyroxine is nonpolar
and can cross the cell membrane. Iodine
deficiency results in goiter and cretinism.
– Thyroxine, is one of two iodine-containing
hormones produced by the thyroid gland.
Epinephrine: Amino Acid Derivative
Hormones
Causes a dramatic
increase in the availability
of glucose as a source of
energy to deal with
whatever stress is at hand.
Epinephrine: Fight-or-Flight
– Initial stimulus to glucose release into the
bloodstream is seconds.
– Hydrophilic: Carried in the bloodstream, binds
to a receptor on the surface of a cell.
– The hormone–receptor complex activates a
nearby G protein in the cell membrane.
Polypeptides are the largest class of
Hormones
•
Thyrotropin-releasing hormone is a modified tripeptide
•
Oxytocin and vasopressin are nonapeptides
•
Insulin is a protein with 51 amino acids
•
Thyroid-stimulating hormone is a protein that has 208
Peptide Hormones
•
•
•
•
Synthesized on the rough ER
Stored in vesicles
Leave signaling cell via exocytosis
Soluble in aqueous solutions and travel to
the target cell dissolved in the extracellular
fluid
• Hydrophilic: cannot cross the target cell
membrane
• Bind to transmembrane receptors
• Rapid effects on the target cell
Molecular Switches: G - Protein Complexes
1. When G protein complexes are
attached to a complex with three
phosphate groups (guanosine
triphosphate [GTP])  They “turn
on”.
2. When they are attached to a
complex with only two phosphate
groups (guanosine diphosphate
[GDP]), they “turn off”.
G-Protein-Coupled Receptors
•
•
•
Transmembrane protein that interacts with intracellular G-proteins
G-proteins – named for their ability to bind guanosine nucleotides
Activate second messengers
Cyclic AMP initiates the activation of
glycogen phosphorylase
• GDP is converted to GTP by addition of a
phosphate group.
• The G protein–GTP complex activates
adenylate cyclase,.
• Adenylate cyclase catalyzes production within
the cell of the second messenger—cyclic
AMP—from ATP
• Glycogen phosphorylases is the enzyme
responsible for release of glucose from storage
• When the emergency has passed, cyclic AMP is
converted back to ATP
Cyclic AMP initiates the activation of
glycogen phosphorylase
Steroid Hormones
• Steroids have in common a central structure
composed of the four connected rings.
• Because they are soluble in hydrophobic
solvents and not in water, steroids are classified
as lipids.
Steroids are Hydrophobic
1. Steroids are lipids (with a distinctive molecular
structure based on four connected rings)
2. Hydrophobic can cross the cell membrane &
receptors inside the cell.
Steroid Hormones
Divided by function into into three types.
1.Mineralocorticoids, regulate the cellular
fluid balance between Na+ and K+ ions
(hence the “mineral” in their name).
2.Glucocorticoids regulate glucose
metabolism and inflammation.
( Anti-inflammatory ointments containing
hydrocortisone reduce the swelling and itching of
poison ivy and other skin irritations).
3.Sex hormones. Regulate the
development of secondary sex
characteristics
Male Sex Hormones
• Testosterone and and Anrosterone.
• Responsible for the development of male
secondary sex characteristics during
puberty and for promoting tissue and
muscle growth.
Female Sex Hormones
1. Estrone and estradiol, govern development of female
secondary sex characteristics and play a major part in
regulation of the menstrual cycle.
2. Progesterone, a progestin, is released during the second
half of the menstrual cycle and prepares the uterus for
implantation of a fertilized ovum.
Transport to the Target Cell
• Hydrophilic (peptide and
amine) messengers
dissolve in aqueous
solutions like extracellular
fluid and blood, bind to
surface receptor, and this
triggers a change in enzyme
activities inside the cell
Hydrophobic
messengers bind
to carrier
proteins in the
blood They then
can bind to
receptors on the
surface – or
inside the cell
Remember the Two Systems For
Messenger Molecules?
Endocrine: 
hormone is
transported by the
circulatory system
 Neural: electrical
signal travels along
a neuron and
releases a
neurotransmitter
Neurotransmitters
• Neurotransmitters are the
chemical messengers of
the nervous system.
• They are released by
nerve cells (neurons) and
transmit signals to
neighboring target cells,
such as other nerve cells,
muscle cells, or endocrine
cells.
Neurotransmitters
• Synapse: The place
where the tip of a neuron
and its target cell lie
adjacent to each other.
Transmission of a nerve signal occurs when a
neurotransmitter is released by the presynaptic
neuron, crosses the synapse, and fits into a
receptor on the postsynaptic neuron.
Neurotransmitters :
Acetylcholine, Agonists and
Antagonists
1. Acetylcholine (ACh) : a
neurotransmitter
responsible for the
control of skeletal
2. muscles.
It is Also widely distributed in the brain, and it thought to play a role in learning, memory, mood
and the sleep/wake cycle.
3.
4.
Nerves that rely on ACh as their neurotransmitter are classified as cholinergic nerves.
Acetylcholine is synthesized in presynaptic neurons and stored in their vesicles.
When a nerve impulse arrives at the presynaptic neuron it initiates a raid sequence of events.
•
•
•
Vesicles move to the cell membrane, fuse, and release their Ach molecules
ACh crosses the synapse and binds to receptors on the postsynaptic neuron.
The binding on the receptors change the permeability to ions, initiating a nerve impulse in the postynaptic
neuron
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• With the message delivered,
acetylcholinesterase present in the synaptic
cleft catalyzes the decomposition of
acetylcholine.
• Choline is absorbed back into the presynaptic
neuron where new ACh is synthesized.
The Hormone / Neurotransmitter Connection
Several hormones synthesized in neurons from
tyrosine (an amino acid derivative) function as
neurotransmitters in the brain.
Link
Link
Chapter Twenty
Acetylcholine: Agonists and Antagonists
• Synthesized in presynaptic neurons and stored
in their vesicles.
• Acetylcholine (ACh) : responsible for the control
of skeletal muscles.
– Also widely distributed in the brain, where it may play
a role in the sleep–wake cycle, learning, memory, and
mood.
• Nerves that rely on ACh as their
neurotransmitter are classified as cholinergic
nerves.
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Action of Drugs on
Acetylcholine
1. A drug is any molecule that alters normal functions when it
enters the body from an external source.
2. Agonists—substances that augment or prolong the normal
response of a receptor.
3. Antagonists—substances that block or inhibit the normal
response of a receptor.
Examples:
• Botulinus toxin (an antagonist), blocks acetylcholine
release and causes botulism.
– The toxin, which is produced by bacterial growth in improperly
canned food, binds irreversibly to the presynaptic neuron, where
acetylcholine would be released.
– It prevents this release, frequently causing death due to muscle
paralysis.
• Black widow spider venom ( agonist), releases
excess acetylcholine the synapse is flooded with
acetylcholine, resulting in muscle cramps and
spasms (Increasing “normal” function”)
• Organophosphorus insecticides (antagonists),
inhibit acetylcholinesterase. Prevents the
cholinesterase enzyme from breaking down
acetylcholine within the synapse. Nerves are
overstimulated.
Nicotine binds to acetylcholine receptors.
– At low doses is a stimulant (an agonist) activating
acetylcholine receptors.
– At high doses, it is an antagonist, irreversibly blocking
acetylcholine receptors and causes their degeneration.
Atropine (an antagonist), competes with
acetylcholine at receptors.
– At controlled doses, it is used to accelerate abnormally
slow heart rates, to cause temporary paralysis of eye
muscles during surgery, or to relax intestinal muscles
in the treatment of gastrointestinal disorders.
– Atropine is also used as I an antidote for
cholinesterase poisons such as organophosphorus
(insecticides). By blocking receptors – it counteracts
the effects of the excess acetylcholine which has been
created by cholinesterase inhibitors.
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Histamine and Antihistamines
Histamine is the neurotransmitter responsible
for the symptoms of the allergic reaction so
familiar to hay fever sufferers or those who are
allergic to animals. It is also the chemical that
causes an itchy bump when an insect bites
you. In the body, histamine is produced by
decarboxylation of the amino acid histidine:
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Pearson Education, Inc.
Chapter Twenty
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• The antihistamines are a family of drugs that
counteract the effect of histamine because
they are histamine receptor antagonists.
• They competitively block the attachment of
histamine to its receptors. Antihistamines have
in common a disubstituted ethylamine side
chain, usually with two N-methyl groups. The
groups at the other end of the molecule tend to
be bulky and aromatic.
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Pearson Education, Inc.
Chapter Twenty
37
Histamine also activates secretion of acid in
the stomach. Development of an antagonist
for this function of histamine was
accomplished by rational drug design. The
result was cimetidine, widely publicized as a
treatment for heartburn under its trade name
of Tagamet.
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Pearson Education, Inc.
Chapter Twenty
38
Histamine and Antihistamines
Histamine is the neurotransmitter responsible for
the symptoms of the allergic reaction of hay fever
& allergy to animals.
It is also the chemical that causes an itchy bump
when an insect bites you. In the body, histamine is
produced by decarboxylation of the amino acid
histidine:
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty
39
• The antihistamines are a family of drugs that
counteract the effect of histamine because they
are histamine receptor antagonists.
• They competitively block the attachment of
histamine to its receptors. Antihistamines have in
common a disubstituted ethylamine side chain,
usually with two N-methyl groups. The groups at
the other end of the molecule tend to be bulky and
aromatic.
Copyright © 2010 Pearson
Education, Inc.
Chapter Twenty
40
Histamine also activates secretion of acid in the
stomach. Development of an antagonist for this
function of histamine was accomplished by
rational drug design. The result was cimetidine,
widely publicized as a treatment for heartburn
under its trade name of Tagamet.
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Education, Inc.
Chapter Twenty
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Serotonin, Norepinephrine, and
Dopamine
• Serotonin, norepinephrine, and dopamine
could be called the “big three” of
neurotransmitters.
• Collectively they are known as monoamines.
• All have been linked to the experience of
extreme moods, experiences of fear, and
pleasure, mental illness, and drug addiction.
• There is a well-established relationship is
the between major depression and a
deficiency of serotonin, norepinephrine,
and dopamine.
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• Drugs used to treat depression all Increases the
concentration of the neurotransmitters at
synapses.
– Amitriptyline prevents the re-uptake of
serotonin and norepinephrine from the
synapse.
– Phenelzine inhibits the enzyme that breaks
down monoamines. This inhibition of MAO
allows the concentrations of monoamines at
synapses to increase.
– Fluoxetine represents the newest class of
antidepressants, the selective serotonin reuptake inhibitors (SSRI). More selective than
tricyclics, they inhibit only the re-uptake of
serotonin.
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• The complex and not yet fully understood
relationships between neurotransmitter activity
and behavior are illustrated by the use of
fluoxetine for conditions other than depression. It
is used to treat:
– obsessive compulsive disorder
-bulimia
– obesity
-PMS
-panic disorder
– body dysmorphic disorder
-teen depression
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• Dopamine plays a role in the brain in
processes that control movement, emotional
responses, and the experiences of pleasure
and pain.
• An oversupply of dopamine is associated with
schizophrenia, and an undersupply results in
the loss of fine motor control in Parkinson’s
disease.
• An ample supply of brain dopamine produces
the pleasantly satisfied feeling that results
from a rewarding experience—a “natural
high.” The more the dopamine receptors are
stimulated, the greater the high.
• Experiments show that cocaine blocks reuptake of dopamine from the synapse, and
amphetamines accelerate release of
dopamine. Studies have linked increased
brain levels of dopamine to alcohol and
nicotine addiction as well.
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Chapter Twenty
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• To maintain homeostasis, the number and
sensitivity of dopamine receptors both
decrease. Brain cells thus require more and
more of a drug for the same result, a
condition that contributes to addiction.
• Marijuana, heroin and cocaine create an
increase in dopamine levels in the same
brain areas. The most active ingredient of the
many in marijuana is tetrahydrocannabinol
(THC).
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Chapter Twenty
46
Neuropeptides and Pain Relief
• The two pentapeptides Met-enkephalin
and Leu-enkephalin were discovered in
the search for animal neurotransmitters
that acted at opiate receptors.
• Met-enkephalin: Tyr-Gly-Gly-Phe-Met
• Leu-enkephalin: Tyr-Gly-Gly-Phe-Leu
• Both exert morphine-like suppression of
pain when injected into the brains of
experimental animals.
• The structural similarity between Met-enkephalin
and morphine, highlighted below, supports the
concept that both interact with the same receptors.
• Subsequently, about a dozen natural pain-killing
polypeptides that act via the opiate receptors have
been found. They are classified as endorphins.
None of these compounds is the long sought ideal,
nonaddicting painkiller—all are addictive.
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Chapter Twenty
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Chapter Summary
• Hormones are the chemical messengers of
the endocrine system. Under control of the
hypothalamus they are released from various
locations, many in response to regulatory
hormones.
• Hormones travel in the bloodstream to target
cells, where they connect with receptors that
initiate chemical changes within cells.
• Hormones are polypeptides, steroids, or
amino acid derivatives.
• Steroids have a distinctive four-ring structure
and are classified as lipids because they are
hydrophobic. All of the sex hormones are
steroids.
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Chapter Twenty
49
Chapter Summary Contd.
• Epinephrine, the fight-or-flight hormone, acts
via proteins that reside in the cell membrane.
The enzyme adenylate cyclase transfers the
message to a second messenger, a cyclic
adenosine monophosphate (cyclic AMP), that
acts within the target cell.
• Neurotransmitters are synthesized in
presynaptic neurons and stored there in
vesicles from which they are released when
needed. They travel across a synaptic cleft to
receptors on adjacent target cells.
• After their message is delivered,
neurotransmitters must be quickly broken
down or taken back into the presynaptic
neuron so that the receptor is free to receive
further messages.
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Chapter Twenty
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Chapter Summary Contd.
• Acetylcholine is released from a presynaptic
neuron and connects with receptors that
initiate continuation of a nerve impulse in the
postsynaptic neuron. It is then broken down
in the synaptic cleft by acetylcholinesterase
to form choline that is recycled.
• Histamine, an amino acid derivative, causes
allergic symptoms. Antihistamines are
antagonists with a general structure that
resembles histamines.
• Monoamines (serotonin, norepinephrine, and
dopamine) are brain neurotransmitters
associated with mental depression and
addiction.
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