CHEMICAL COMMUNICATION
HORMONES &
NEUROTRANSMITTERS
Introduction
• There are three principal types of molecules
used for communications
– Receptors: proteins embedded in the surface
membranes of cells
– Chemical messengers: chemicals that interact
with receptors; also called ligands
– Secondary messengers: chemicals that carry a
message from a receptor to the inside of a cell
and amplify the message
A large percent of drugs used in human medicine
influence chemical communication (see Table 23.1)
- antagonist: a molecule that blocks a natural receptor
and prevents its stimulation
- agonist: a molecule that competes with a natural
messenger for a receptor site; it binds to the receptor site
and elicits the same response as the natural messenger
- a drug may decrease (by controlling its release) or
increase (by inhibiting its removal from receptors) the
effective concentration of messenger
Other terms and definitions
neuron: a nerve cell
neurotransmitter: a compound involved in
communication between neurons or between a
neuron and a target tissue; it acts across a synapse
hormone: a compound that is synthesized in one
location, travels large distances, usually in the
blood, and then acts at a remote location (see Table
23.2).
The distinction between a neurotransmitter and
a hormone is physiological, not chemical; it
depends on whether the molecule acts over a
short distance (across a synapse) or over a long
distance (from the secretory organ, through the
blood, to its site of action)
Neuron and synapse
Fig. 23.1, p.573
• There are five classes of chemical messengers:
• cholinergic messengers
• amino acid messengers
• adrenergic messengers
• peptidergic messengers
• steroid messengers
• Messengers are also classified by how they
work; they may
– activate enzymes
– affect the synthesis of enzymes
– affect the permeability of membranes
– act directly or through a secondary messenger
CLASSES OF CHEMICAL MESSENGERS
Cholinergic - acetylcholine – neurotransmitter,
transfers nerve impulse to muscle cells
Amino acid – simple amino acids & modified amino
acids – neurotransmitters
Adrenergic - monoamines similar to epenephrine
(adrenalin) - neurotransmitters & hormones
Peptidergic – peptides & proteins – neurotransmitters &
hormones
Steroid - steroids - hormones & neurotransmitters
ACETYLCHOLINE
Acetylcholine
• The main cholinergic messenger is
acetylcholine
• Cholinergic receptors
– there are two kinds of receptors for
acetylcholine
– we look at the one that exists in motor end
plates of skeletal muscles or in sympathetic
ganglia
Acetylcholine – synthesized in
presynaptic cell, stored in vesicles.
Release is triggered by the buildup of
Ca2+ ions.
Acetylcholine moves across the
synapse & forms a complex with
receptor. Opens a channel for ion flow
& creates a flow of charge by
exchanging Na+ and K+ - this
constitutes a nerve impulse.
Acetylcholine is broken down &
removed from the receptor by
acetylcholinesterase.
• Storage and release of acetylcholine (ACh)
– the message is initiated by calcium ions, Ca2+
– the nerve cells that bring messages contain ACh
stored in vesicles
– when Ca2+ concentration becomes more that
about 10-4 M, the vesicles that contain ACh
fuse with the presynaptic membrane of nerve
cells and empty ACh into the synapse
– ACh travels across the synapse and is absorbed
on specific receptor sites
Chem Connect 23A, p.578
• Action of the acetylcholine (cont’d)
– the presence of ACh on the postsynaptic
receptor triggers a conformation change in the
receptor protein
– this change opens an ion channel and allows
ions to cross membranes 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
Acetylcholine
Acetylcholine
• Removal of ACh
– ACh is removed from the receptor site by
hydrolysis catalyzed by the enzyme
acetylcholinesterase
this rapid removal allows nerves to transmit more
than 100 signals per second
• Control of neurotransmission
– acetylcholinesterase is inhibited irreversibly by
the phosphonates in nerve gases and some
pesticides (ChemCom 23B)
– it is also inhibited by these two compounds
• Control of transmission (cont’d)
– 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 attachment 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 high doses is an antagonist and
blocks the action of the receptor
Amino Acids
• Amino acid messengers
– some amino acids are excitatory
neurotransmitters; examples are Glu, Asp, and
Cys
– others are inhibitory neurotransmitters;
examples are Gly and these three
Amino Acid Messengers
• Receptors
– Glu has at least five subclasses of receptors
– the best known among these is the N-methyl-D-
aspartate (NMDA) receptor
– this receptor is a ligand-gated ion channel
– when Glu binds to the receptor, the ion channel
opens, Na+ and Ca2+ ions flow in, and K+ ions
flow out NMDA is an agonist and also
stimulates the receptor
Adrenergic Messengers
• Monoamine messengers
G protein hydrolyzes
GTP,activating adenylate
cyclase which forms cAMP
cAMP activates protein
kinase; ATP phosphorylates
catalytic unit
Catalytic unit
phosphorylates ion-
translocating protein, &
opens ion gates.
Adrenergic Messengers
• When norepinephrine is absorbed onto the
receptor site
– the active G-protein hydrolyzes GTP
– the energy of hydrolysis activates adenylate
cyclase
Cyclic AMP (cAMP)
– cAMP is synthesized in cells from ATP
Adrenergic Messengers
– cyclic AMP activates protein kinase by
dissociating the regulatory (R) unit from the
catalytic (C) unit
Adrenergic Messengers
– the catalytic unit phosphorylates the ion-
translocating protein that blocks the channel ion
flow
– the phosphorylated ion-translocating protein
changes its shape and position and opens the
ion gate
Adrenergic Messengers
• Removal of the signal
– when the neurotransmitter or hormone
dissociates from the receptor, 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
Adrenergic Messengers
• Control of neurotransmission
– the G-protein-adenylate cyclase cascade in
transduction signaling is not limited to
monoamine messengers
– among the other neurotransmitters and peptide
hormones using this signaling pathway are
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 are active or
inactive
Adrenergic Messengers
• Removal of neurotransmitter
– the body inactivates monoamines by oxidation
to an aldehyde, catalyzed by monoamine
oxidases (MAOs)
• Histamine
– 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
• 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
• Neuropeptide Y, a potent orexic, affects the
hypothalamus
• Substance P, an 11-amino acid peptide is
involved in the transmission of pain signals
Peptidergic Messengers
• All peptidergic messengers, hormones, and
neurotransmitters act through secondary
messengers
– glucagon, luteinizing hormone, antidiuretic
hormone, angiotensin, enkephalin, and
substance P use the G-protein-adenylate cyclase
cascade. Others such as vasopressin use
membrane-derived phosphatidylinositol (PI)
derivatives
Steroid 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
Modes of hormone action
Activate enzymes ex. – epinephrine
Alter gene transcription & the synthesis
of enzymes ex. – steroids
Alter the permeability of membranes ex. -
insulin