196 Chapter 7
suggested that the effects of these drugs might be due to the
stimulation of specific neuron pathways. This implied that
opioids—along with LSD, mescaline, and other mind-altering
drugs—might mimic the actions of neurotransmitters produced
by the brain.
The analgesic effects of morphine are blocked in a specific
manner by a drug called naloxone. In the same year that opioid
receptor proteins were discovered, it was found that naloxone
also blocked the analgesic effect of electrical brain stimulation.
Polypeptides as Neurotransmitters
Many polypeptides of various sizes are found in the synapses
of the brain. These are often called neuropeptides and are
believed to function as neurotransmitters. Interestingly, some
of the polypeptides that function as hormones secreted by
the small intestine and other endocrine glands are also pro-
duced in the brain and may function there as neurotransmit-
ters ( table 7.7 ). For example, cholecystokinin (CCK), which is
secreted as a hormone from the small intestine, is also released
from neurons and used as a neurotransmitter in the brain.
Recent evidence suggests that CCK, acting as a neurotrans-
mitter, may promote feelings of satiety in the brain following
meals. Another polypeptide found in many organs, substance
P, functions as a neurotransmitter in pathways in the brain that
mediate sensations of pain.
Some neurons in both the PNS and the CNS produce both
a classical neurotransmitter (ACh or a catecholamine) and a
polypeptide neurotransmitter. These are contained in different
synaptic vesicles that can be distinguished using the electron
microscope. The neuron can thus release either the classical
neurotransmitter or the polypeptide neurotransmitter under dif-
ferent conditions.
Endogenous Opioids
The ability of opium and its analogues—the opioids —to
relieve pain (promote analgesia) has been known for centuries.
Morphine, for example, has long been used for this purpose.
The discovery in 1973 of opioid receptor proteins in the brain
CLINICAL APPLICATION
Benzodiazepines, including Valium and Xanax, were devel-
oped to treat anxiety and promote sleep. These drugs
bind to a subgroup of GABA receptors, thereby increasing
their permeability to Cl^2 when these receptors also bind
to GABA. The increased inflow of Cl^2 into the postsynap-
tic neuron enhances the inhibitory effect of GABA at their
synapses in the brain and spinal cord. Benzodiazepines,
acting through inhibitory effects on spinal motoneurons that
innervate skeletal muscles, are also widely used to treat the
muscle spasms of epilepsy and other causes of seizures.
Clinical Investigation CLUES
Denise had a prescription for Xanax to treat her anxiety
and help her sleep.
- What is the mechanism of action of Xanax and other
benzodiazepines? - How would the benzodiazepines be beneficial in
treating Denise’s seizure?
Table 7.7 | Examples of Chemicals
That Are Either Proven or Suspected
Neurotransmitters
Category Chemicals
Amines Histamine
Serotonin
Catecholamines Dopamine
(Epinephrine—a hormone)
Norepinephrine
Choline derivative Acetylcholine
Amino acids Aspartic acid
GABA (gamma-aminobutyric acid)
Glutamic acid
Glycine
Polypeptides Glucagon
Insulin
Somatostatin
Substance P
ACTH (adrenocorticotrophic hormone)
Angiotensin II
Endogenous opioids (enkephalins and
endorphins)
LHRH (luteinizing hormone-releasing
hormone)
TRH (thyrotrophin-releasing hormone)
Vasopressin (antidiuretic hormone)
CCK (cholecystokinin)
Lipids Endocannabinoids
Gases Nitric oxide
Carbon monoxide
Purines AT P