Human Physiology, 14th edition (2016)

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