CHEMICAL COMMUNICATIONS: NEUROTRANSMITTERS
AND HORMONES
24-1 HOW DO CELLS COMMUNICATE?
3 PRINCIPAL TYPES OF MOLECULES FOR
COMMUNICATION
1. RECEPTORS – protein molecules that bind to
ligands and effect some type of change.
• They may be on the surface of the cells,
embedded in the membrane of the
subcellular organelles, or free in solution
2. CHEMICAL MESSENGERS – also called ligands,
interact with the receptors
• Chemical messengers fit into the
receptor sites in a manner reminiscent
of the lock-and-key model
3. SECONDARY MESSENGERS – in many cases carry
the cases from the receptor to the inside of the
cell and amplify the message.
TERMS AND DEFINITION
NEURONS – nerve cells; present throughout the body
and together with the brain, constitute the nervous
system
• In the neurons, the signals travel as electric
impulses along the axons
• When they reach the end of the neuron, the
signals are transmitted to adjacent neurons y
specific compounds called neurotransmitters
NEUROTRANSMITTERS – chemical messengers between
a neuron and another target cell; a neuron, muscle cell
or a cell of a gland
HORMONE – chemical messenger releases by an
endocrine gland into the blood stream ad transported in
the blood to reach its target cell
24-2 WHAT IS THE DIFFERENCE BETWEEN
NUEROTRANSMITTER AND A HORMONE?
NEUROTRANSMITTERS – are compounds that
communicate between 2 nerve cells or between a nerve
cell and another cell.
• A nerve cell consists of a main cell body from
which projects a long, fiber-like part called axon
• Coming off the other side of the main body are
hair-like structures called dendrites
• Between the axon end of one neuron and the cell
body or dendrite end of the next neuron is a
space filled with an aqueous fluid called a
synapse
o If the chemical signal travels, from axon
to dendrite, we call the nerve ends on
the axon the presynaptic site
• The neurotransmitters are stored at the
presynaptic site in vesicles, which are small,
membrane-enclosed packages
• Receptors are located in the postsynaptic site of
the cell body or the dendrite
HORMONES – are diverse compounds secreted by
specific tissues, released in the bloodstream, and then
adsorbed onto specific receptor sites
➔ The distinction between hormones and
neurotransmitters is physiological not chemical.
Whether a certain compound is considered to be
a neurotransmitter or a hormone depends on
whether it acts over a short distance across a
synapse, in which case a neurotransmitter, or
over long distance from the secretory gland
through the bloodstream to the target cell, in
which case it is a hormone
➔ Epinephrine and norepinephrine are both a
neurotransmitter and a hormone
5 CLASSES OF CHEMICAL MESSENGER
1. Cholinergic
2. Amino acid
3. Adrenergic
4. Peptidergic
5. Steroid messengers
➔ Neurotransmitters can belong to all classes, and
hormones can belong to the last 3 classes
Chemical messengers are also classified by how they
A work; they may:
• Activate enzymes
• Affect the synthesis of enzymes
• Affect the permeability of membranes
• Act directly or through a secondary messenger
CHEMICAL COMMUNICATIONS
• A large percentage of the drugs we encounter in
medical practice try to influence chemical
communications. A drug may affect either a
messenger, a receptor, a secondary messenger,
 or an enzyme that is activated or inactivated as
part of a metabolic pathway
• An antagonist drug blocks a receptor and
prevents its stimulation
• An agonist drug competes with a natural
messenger for a receptor site. Once there it
stimulates the receptor
• Other drugs increase the concentration of a
messenger by inhibiting its removal from its
receptors.
• Still other drugs inhibit or activate specific
enzymes inside cells.
24-3 HOW DOES A CHOLINERGIC MESSENGER WORK?
ACETYLCHOLINE – the main cholinergic
neurotransmitter
A. CHOLINERGIC RECEPTORS
• Exists on the motor end plates of
skeletal muscles or in sympathetic
ganglia
• The receptor itself is a transmembrane
protein made of 5 different subunits
• The central core of the receptor is an
ion channel through which, when open,
Na+ and K+ ions can pass. When ion
channels are closed, the K+ ion
concentration is higher inside the cell
than outside; the Na+ ion concentration
is higher outside of the cell than inside
B. STORAGE OF MESSENGERS
• Events begin when a message is
transmitted from one neuron to the next
by neurotransmitters. The message is
initiated by calcium ions.
• When the concentration in a neuron
reaches a certain level (more than
0.1uM), the vesicles containing ACh
(Acetylcholine) fuse with the presynaptic
membrane of the nerve cells.
• Then they empty the neurotransmitters
into the synapse. The messenger
molecules travel across the synapse and
are adsorbed onto specific receptor
sites.
C. CALCIUM AS SIGNALLING AGENT (Secondary
messenger)
• The message delivered to the receptors
on the cell membrane by
neurotransmitters or hormones must be
delivered intracellularly to various
locations within the cell
• The most universal yet most versatile
signaling agent is the cation Ca+
• Calcium ion signaling controls different
functions via 2 mechanisms: (1)
increased concentration and (2)
duration of signals
• Source of calcium ions may be external
(calcium influx caused by the electrical
signal of nerve transmission) or internal
(calcium released from the stores of the
endoplasmic reticulum
• The effects of Ca+ are modulated
through specific calcium-binding
proteins. In all non-muscle cells and in
smooth muscles, calmodulin serve as
the calcium-binding protein
• Calmodulin-bound calcium activates an
enzyme, protein kinase II, which then
phosphorylates an appropriate protein
substrate. In this way, the signal is
translated into metabolic activity
SUMMARY OF STORAGE AND RELEASE OF ACH
D. ACTION OF MESSENGERS
• The presence of Ach molecules at the
postsynaptic receptor site triggers a
conformational change in the receptor
protein.
• This opens the ion channel, and allows
ions to cross membrane freely
 • Na+ ions have higher concentration
outside the neuron and pass into it.
• K+ ions have higher concentration
inside the neuron and leave it.
• This change of Na+ and K+ ion
concentrations is translated into a nerve
signal
• After a few milliseconds, the ion channel
closes
➔ For the channel to reopen and transmit a new
signal, Ach must be removed and the neuron
must be activated
E. THE REMOVAL OF MESSENGERS
• ACh is removed from a receptor site by
hydrolysis catalyzed by the enzyme
acetylcholinesterase.
• This rapid removal allows nerves to
transmit more than 100 signals per
second.
• When Ach-esterase is inhibited, removal
of Ach is incomplete thus nerve
transmission ceases
CONTROL OF NEUTRANSMISSION
• Acetylcholinesterase is inhibited irreversibly by
the phosphonates in nerve gases and some
pesticides.
• It is inhibited by succinylcholine and
decamethonium bromide (muscle relaxant)
• Succinylcholine and decamethonium bromide
resemble the choline end of the Ach and
therefore acts a competitive inhibitor
• Inhibition of acetylcholinesterase is one way of
controlling cholinergic formation
• Another control is to modulate the action of the
ACh receptor.
• Because ACh enables ion channels to open and
propagate signals, the channels themselves are
called ligand-gated ion channels.
• The binding of the ligand to the receptor is
critical to signaling.
• Nicotine in low doses is a stimulant; it is an
agonist because it prolongs the receptor’s
biochemical response.
• Nicotine in large doses is an antagonist and
blocks the action of the receptor and may cause
convulsions and respiratory paralysis
• Strong antagonist which blocks the receptor
completely can interrupt the communication
between neuron and muscle cell
o Cobratoxin – found in venom of snakes
o Curare – found in poisoned arrow of
Amazon Indians; may acts as a muscle
relaxant in small doses
• Supply of Ach can influence the proper nerve
transmission, concentration of Ach is reduced
and nerve transmission is impaired:
o Botulism – Ach is not released
o Alzheimer’s disease – synthesis is
impaired
24-4 WHAT AMINO ACIDS ACT AS
NEUROTRANSMITTERS?
AMINO ACID MESSENGERS
• Some AA are excitatory neurotransmitters; Glu,
Asp, and Cys
• Others are inhibitory neurotransmitters (reduce
transmission); Gly, Taurine, b-Alanine, y-
Aminobutyric acid (GABA)
Each amino acid has its own receptors:
• Glu has at least five subclasses of receptors.
• The best-known receptor of Glu is the N-methyl-
D-aspartate (NMDA) receptor. This receptor is a
ligand-gated ion channel.
• Phencyclidine – antagonist to AA receptor,
induces hallucinations, “angel dust”, causes
bizarre psychotic behavior and long-term
psychological problems
• When Glu binds to the receptor, the ion channel
opens, Na+ and Ca2+ ions flow in, and K+ ions
flow out.
• The gate of this channel is closed by Mg2+ ion.
• There is no enzyme to degrade Glu to remove it
from its receptor once signaling has occurred
• Glu is removed by reuptake, which is facilitated
by transporter molecules.
o Glu is removed by a transporter, which
brings it back through the presynaptic
membrane (reuptake)
 o Transporter – protein molecule that
carries small molecules across a
membrane
24-5 WHAT ARE ADRENERGIC MESSENGERS?
• Examples are epinephrine, norepinephrine,
serotonin, dopamine and histamine
MONOAMINE MESSENGERS
• These monoamines transmit signals by a
mechanism whose beginning is similar to the
action of acetylcholine, that is, they are absorbed
on a receptor
• Once the monoamine is adsorbed onto the
receptor, the signal is amplified inside the cell
• G-protein – produces many signal (amplification)
CYCLIC AMP (cAMP)
• cAMP is synthesized in cells from ATP
• act as secondary messenger which amplifies the
signal
➔ The catalytic unit phosphorylates the ion-
translocating protein that blocked the channel ion
flow.
➔ The phosphorylated ion-translocating protein
changes its shape and position and opens the ion
gate.
REMOVAL OF SIGNAL
• When the neurotransmitter or hormone
dissociates from the receptor, the adenylate
cyclase stops the synthesis of cAMP.
• The cAMP already produced is destroyed by the
enzyme phosphodiesterase, which catalyzes the
hydrolysis of one of the phosphodiester bonds to
give AMP.
• The amplification through the secondary
messenger (cAMP) is relatively slow. It may take
from 0.1 s to a few minutes.
• In cases where transmission must be fast, a
neurotransmitter, such as acetylcholine, acts on
membrane permeability directly without a
second messenger.
CONTROL OF NEUROTRANSMISSION
• G-protein—adenylate cyclase cascade in
transduction signaling is not limited to
monoamine messengers
• A variety of other neurotransmitters and peptide
hormones use this signaling pathway, including
glucagon, vasopressin, luteinizing hormone,
enkephalins, and P-protein
• A number of enzymes can be phosphorylated by
protein kinases and the phosphorylation
controls whether these enzymes will be active or
inactive
REMOVAL OF NEUROTRANSMITTER
• The body inactivates monoamines by oxidation
to an aldehyde, catalyzed by monoamine
oxidases (MAOs).
• The action of histamine is similar to that of other
monoamines. It is synthesized from His by
decarboxylation.
• H1 receptors are found in the respiratory tract
where they affect the vascular, muscular, and
secretory changes associated with hay fever and
asthma; antihistamines that block H1 receptors
relieve these symptoms.
• H2 receptors are found mainly in the stomach
and affect the secretion of HCl; cimetidine and
ranitidine block H2 receptors and thus reduce
acid secretion.
24-6 WHAT IS THE ROLE OF PEPTIDES IN CHEMICAL
COMMUNICATION?
PEPTIDERGIC MESSENGERS
• The first brain peptides isolated were the
enkephalins
• These pentapeptides are present in certain
nerve cell terminals.
• They bind to specific pain receptors and seem to
control pain perception.
• Because they bind to the receptor site that also
binds the pain-killing alkaloid morphine, it is
assumed that the N-terminal binds to the
receptor
o Morphine – most effective agent in
reducing pain
o Side effects: respiratory depression,
constipation and addiction
 • Neuropeptide Y – affects the hypothalamus 3. Other drugs decrease the concentration of the
(integrates hormonal and nervous system); a messenger by controlling the release of
potent orexic (appetite-stimulating) agent messengers from their storage
• Leptin – “thin protein” anorexic agent 4. Other drugs increase the concentration of the
• Substance P – involved in the transmission of messenger by inhibiting its removal from the
pain signal receptors
5. Others act to hibit or activate specific enzymes
FLOW inside the cell
Injury/inflammation → Sensory fibers (transmit signals)
→ PNS (synthesize and release substance P) → CNS
(spinal cord) process pain → Substance P removes the
magnesium block at the N-methyl-D-aspartate receptor
→ Glu can bind to the receptor, amplifying the pain
signal to the brain

GLUCAGON ACTION

• Phophofructose-kinase-2: decreases activity →

glycolysis
• Fructose-biphosphatase-2: increases activity --?
Gluconeogenesis

24-7 HOW DO STEROID HORMONES ACT AS

MESSENGERS?

A large number of hormones are steroids.

• These hormones are hydrophobic and,

therefore, cross plasma membranes by diffusion.
• Steroid hormones interact inside cells with
protein receptors.
• Most of these receptors are located in the
nucleus, but small numbers also exist in the
cytoplasm.
• Once inside the nucleus, the steroid-receptor
complex can either bind directly to DNA or
combine with a transcription factor, a protein
that binds to DNA and alters the expression of a
gene, thereby influencing the synthesis of
certain key proteins.

24-8 HOW DO DRUGS AFFECT CHEMICAL

COMMUNICATION?

WAYS THESE DRUGS ACT IN THE BODY:

1. An antagonist drug blocks the receptor and

prevent its stimulation
2. An agonist drug competes with the natural
messenger for the receptor site, once there, it
stimulates the receptor