NSCELEC 3 BIOLOGICAL CHEMISTRY

WEEK 9
NEUROTRANSMITTER AND HORMONES

Neurotransmitters and hormones are two different types of chemicals that carry signals from one
part of the body to another. Both chemicals play an important part in the body’s physiology. They
control a variety of physical and psychological functions, including our mood, our eating patterns,
our ability to learn, and our sleep cycles.
Both hormones and neurotransmitters influence our thoughts and motivations, as well as our
ability to learn and concentrate. However, neurotransmitters’ actions are short-lived while
hormones act for longer periods of time. Furthermore, neurotransmitters can affect both voluntary
actions (eating, bathing, walking) and involuntary actions (breathing, blinking). Hormones in the
endocrine system always work involuntarily.

OBJECTIVES:

At the end of this module, you should be able to:

1. Define neurotransmitter and hormone;
2. Identify the molecules involved in chemical communication and;
3. Explain the importance of cell communication.

NEUROTRANSMITTERS
Neurotransmitters are chemical messengers that transmit a signal from a neuron
across the synapse to a target cell, which can be a different neuron, muscle cell, or gland
cell. Neurotransmitters are chemical substances made by the neuron specifically to
transmit a message.
 Illustrations by Elizabeth A. Weaver II

Neurotransmitters are stored in synaptic vesicles, clustered close to the cell

membrane at the axon terminal of the presynaptic neuron. Neurotransmitters are released
into and diffuse across the synaptic cleft, where they bind to specific receptors on the
membrane of the postsynaptic neuron. Binding of neurotransmitters may influence the
postsynaptic neuron in either an excitation or inhibitory way, depolarizing or repolarizing
it respectively.

Examples of Important Neurotransmitter Actions

As explained above, the only direct action of a neurotransmitter is to activate a
receptor. Therefore, the effects of a neurotransmitter system depend on the connections
of the neurons that use the transmitter, and the chemical properties of the receptors that
the transmitter binds to.

Here are a few examples of important neurotransmitter actions:

1. Glutamate is used at the great majority of fast excitatory synapses in the brain and
spinal cord. It is also used at most synapses that are "modifiable", i.e. capable of
increasing or decreasing in strength. Modifiable synapses are thought to be the
main memory-storage elements in the brain.
2. GABA is used at the great majority of fast inhibitory synapses in virtually every part
of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of
GABA. Correspondingly, glycine is the inhibitory transmitter in the spinal cord.
3. Acetylcholine was the first neurotransmitter discovered in the peripheral and
central nervous systems. It activates skeletal muscles in the somatic nervous
system and may either excite or inhibit internal organs in the autonomic system.
4. Dopamine has important functions in the brain; this includes regulation of motor
behavior, pleasures related to motivation and also emotional arousal. It plays a
critical role in the reward system.
5. Norepinephrine which is synthesized in the central nervous system and
sympathetic nerves, modulates the responses of the autonomic nervous system,
the sleep patterns, focus and alertness.
 6. Epinephrine which is also synthesized from tyrosine is released in the adrenal
glands and the brainstem. It plays a role in sleep, with one's ability to become and
stay alert, and the fight-or-flight response.
7. Histamine works with the central nervous system (CNS), specifically the
hypothalamus (tuberomammillary nucleus) and CNS mast cells.

HORMONES

A hormone (from the Greek participle ὁρμῶν, "setting in motion") is any member
of a class of signaling molecules in multicellular organisms, that are transported to distant
organs to regulate physiology and / or behavior. Hormones are required for the correct
development of animals, plants and fungi. The lax definition of a hormone (as a signaling
molecule that acts distant from its site of production) means that many different classes
of molecule can be defined as hormones.

Hormones are used to communicate between organs and tissues. In invertebrates,

hormones are responsible for the regulation of many physiological processes and
behavioral activities such as digestion, metabolism, respiratory, sensory perception,
sleep, excretion, lactation, stress induction, growth and development, reproduction, and
mood manipulation.

EFFECTS IN HUMANS
Hormones have the following effects on the body:

• stimulation or inhibition of growth

• wake-sleep cycle and other circadian rhythms
• mood swings
• induction or suppression of apoptosis (programmed cell death)
• activation or inhibition of the immune system
• regulation of metabolism
• preparation of the body for mating, fighting, fleeing, and other activity
• preparation of the body for a new phase of life, such as puberty, parenting, and
menopause
• control of the reproductive cycle
• hunger cravings

COMPARISON WITH NEUROTRANSMITTERS

There are various clear distinctions between hormones and neurotransmitters:

• A hormone can perform functions over a larger spatial and temporal scale than can
a neurotransmitter.
• Hormonal signals can travel virtually anywhere in the circulatory system, whereas
neural signals are restricted to pre-existing nerve tracts.
 • Assuming the travel distance is equivalent, neural signals can be transmitted much
more quickly (in the range of milliseconds) than can hormonal signals (in the range
of seconds, minutes, or hours). Neural signals can be sent at speeds up to 100
meters per second.
• Neural signaling is an all-or-nothing (digital) action, whereas hormonal signaling is
an action that can be continuously variable as dependent upon hormone
concentration.

Neurohormones are a type of hormone that are produced by endocrine cells that
receive input from neurons, or neuroendocrine cells. Both classic hormones and
neurohormones are secreted by endocrine tissue; however, neurohormones are the result
of a combination between endocrine reflexes and neural reflexes, creating a
neuroendocrine pathway.

TYPES OF HORMONES
Maintaining homeostasis within the body requires the coordination of many
different systems and organs. Communication between neighboring cells, and between
cells and tissues in distant parts of the body, occurs through the release of chemicals
called hormones. Hormones are released into body fluids (usually blood) that carry these
chemicals to their target cells. At the target cells, which are cells that have a receptor for
a signal or ligand from a signal cell, the hormones elicit a response. The cells, tissues,
and organs that secrete hormones make up the endocrine system.

1. Lipid-Derived Hormones (or Lipid-Soluble Hormones)

Most lipid hormones are derived from cholesterol and thus are structurally similar,
as illustrated in Figure 1. The primary class of lipid hormones in humans is the steroid
hormones. Chemically, these hormones are usually ketones or alcohols; their chemical
names will end in “-ol” for alcohols or “-one” for ketones. Examples of steroid hormones
include estradiol, which is an estrogen, or female sex hormone, and testosterone, which
is an androgen, or male sex hormone. These two hormones are released by the female
and male reproductive organs, respectively. Other steroid hormones include aldosterone
and cortisol, which are released by the adrenal glands along with some other types of
androgens.

The structures shown here represent (a) cholesterol, plus the steroid hormones (b) testosterone and (c)
estradiol.
2. Amino Acid-Derived Hormones
The amino acid-derived hormones are relatively small molecules that are derived
from the amino acids: tyrosine and tryptophan, shown in Figure 2. If a hormone is amino
acid-derived, its chemical name will end in –ine. Examples of amino acid-derived
hormones include epinephrine and norepinephrine, which are synthesized in the medulla
of the adrenal glands, and thyroxine, which is produced by the thyroid gland. The pineal
gland in the brain makes and secretes melatonin which regulates sleep cycles.

(a) The hormone epinephrine, which triggers the fight-or-flight response, is derived from the amino acid
tyrosine. (b) The hormone melatonin, which regulates circadian rhythms, is derived from the amino acid
tryptophan.

3. PEPTIDE HORMONES
The structure of peptide hormones is that of a polypeptide chain (chain of amino
acids). The peptide hormones include molecules that are short polypeptide chains, such
as antidiuretic hormone and oxytocin produced in the brain and released into the blood in
the posterior pituitary gland. This class also includes small proteins, like growth hormones
produced by the pituitary, and large glycoproteins such as folliclestimulating hormone
produced by the pituitary. Figure 3 illustrates these peptide hormones.

Figure 3. The structures of peptide hormones (a) oxytocin, (b) growth hormone, and (c) follicle-stimulating
hormone are shown. These peptide hormones are much larger than those derived from cholesterol or
amino acids.

CHEMICAL COMMUNICATION

Chemical communication is a universal feature of life that occurs at all levels of

biological organization, including regulation of cells and organs within the body, as well
as social behavior and ecological interactions among individuals.
 While the necessity for cellular communication in larger organisms seems obvious,
even singlecelled organisms communicate with each other. The ability of cells to
communicate through chemical signals originated in single cells and was essential for the
evolution of multicellular organisms. The efficient and errorfree function of communication
systems is vital for all forms of life.
FORMS OF SIGNALING
There are four categories of chemical signaling found in multicellular organisms.
The main difference between the different categories of signaling is the distance that the
signal travels through the organism to reach the target cell. It is also important to note that
not all cells are affected by the same signals.

1. Endocrine- acts on the target cells after being released into the bloodstream.
2. Paracrine- acts on the nearby cells and does not have to enter the general
circulation.
3. Autocrine- affects the cell types that secreted it and causes a biological effect.
4. Intacrine- acts intercellularly on the cells that synthesized it.

TYPES OF RECEPTORS
Receptors are protein molecules in the target cell or on its surface that bind ligands.

1. Internal Receptors- Internal receptors, also known as intracellular or cytoplasmic

receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand
molecules that travel across the plasma membrane.

Intracellular Receptors: Hydrophobic signaling molecules typically diffuse across the plasma membrane
and interact with intracellular receptors in the cytoplasm. Many intracellular receptors are transcription
factors that interact with DNA in the nucleus and regulate gene expression.
2. Cell-Surface Receptors- Cell-surface receptors, also known as transmembrane
receptors, are cell surface, membrane-anchored, or integral proteins that bind to external ligand
molecules. This type of receptor spans the plasma membrane and performs signal transduction,
converting an extracellular signal into an intracellular signal.

3. Ion Channel-Linked Receptors- Ion channel-linked receptors bind a ligand and open a
channel through the membrane that allows specific ions to pass through. To form a channel, this
type of cell-surface receptor has an extensive membrane-spanning region.

Gated-Ion Channels: Gated ion channels form a pore through the plasma membrane that opens when the
signaling molecule binds. The open pore then allows ions to flow into or out of the cell.

4. G-Protein Linked Receptors- G-protein-linked receptors bind a ligand and activate a

membrane protein called a G-protein. The activated G-protein then interacts with either an ion
channel or an enzyme in the membrane. All G-protein-linked receptors have seven
transmembrane domains, but each receptor has its own specific extracellular domain and
Gprotein-binding site.

G-proteins: Heterotrimeric G proteins have three subunits: α, β, and γ. When a signaling molecule binds to a
G-protein-coupled receptor in the plasma membrane, a GDP molecule associated with the α subunit is
exchanged for GTP.
 5. Enzyme-Linked Receptors
Enzyme-linked receptors are cell-surface receptors with intracellular domains that
are associated with an enzyme. In some cases, the intracellular domain of the receptor
itself is an enzyme or the enzyme linked receptor has an intracellular domain that interacts
directly with an enzyme. The enzyme-linked receptors normally have large extracellular
and intracellular domains, but the membrane-spanning region consists of a single alpha-
helical region of the peptide strand. When a ligand binds to the extracellular domain, a
signal is transferred through the membrane and activates the enzyme, which sets off a
chain of events within the cell that eventually leads to a response.

ACETYLCHOLINE AS MESSENGER
Acetylcholine, an ester of choline and acetic acid that serves as a transmitter
substance of nerve impulses within the central and peripheral nervous systems.
Acetylcholine is the chief neurotransmitter of the parasympathetic nervous system, the
part of the autonomic nervous system (a branch of the peripheral nervous system) that
contracts smooth muscles, dilates blood vessels, increases bodily secretions, and slows
heart rate. Acetylcholine can stimulate a response or block a response and thus can have
excitatory or inhibitory effects.

Acetylcholine Secretion and Reabsorption

AMINO ACID NEUROTRANSMITTER

The amino acid neurotransmitters are common neurotransmitters in the central
nervous system. Glycine, glutamate, and GABA are classed under amino acid
neurotransmitter. The two amino acids functioning as excitatory neurotransmitter are
glutamate and aspartate. GABA acts as a brake to the excitatory neurotransmitters, and
thus when it is abnormally low, this can lead to anxiety, and glutamate usually ensures
homeostasis with the effects of GABA. Excitatory neurotransmitters function to activate
the receptors on the postsynaptic membrane and enhance the effects of action potential,
while inhibitory neurotransmitter functions in a reverse mechanism.
 The glutamate synapse

STERIOD HORMONES AS MESSENGER

Steroid hormones (SHs) are lipophilic molecules derived from cholesterol and
synthesized in the adrenal cortex (glucocorticoids, mineralocorticoids, and adrenal
androgens), the testes (testicular androgens, oestrogen), and the ovary and placenta
(oestrogens and progestagens or progestins). Steroid hormones reach their target cells
via the blood, where they are bound to carrier proteins, and because of their lipophilic
nature pass the cell membrane by simple diffusion. Within the target cells SHs bind to
steroid hormone receptors (SHRs), the key mediators of SH action, which are complexed
to chaperones that help other proteins to fold and prevent aggregation.