Human Physiology, 14th edition (2016)

The Nervous System 189

There are five subtypes of muscarinic ACh receptors,
dubbed M1 through M5, producing different effects in dif-
ferent organs. For example, the M2 subtype causes slow-
ing of the heart and the M3 subtype causes relaxation of
the pulmonary bronchioles (airways). These differences
have been exploited in the design of drugs that minimize
side effects by being relatively specific for the muscarinic
subtype.

Acetylcholinesterase (AChE)

The bond between ACh and its receptor protein exists for
only a brief instant. The ACh-receptor complex quickly dis-
sociates but can be quickly re-formed as long as free ACh is
in the vicinity. In order for activity in the postsynaptic cell
to be stopped, free ACh must be inactivated very soon after
it is released. The inactivation of ACh is achieved by means
of an enzyme called acetylcholinesterase, or AChE, which
is present on the postsynaptic membrane or immediately out-
side the membrane, with its active site facing the synaptic
cleft ( fig. 7.28 ). AChE hydrolyzes acetylcholine into acetate
and choline, which can then reenter the presynaptic axon ter-
minals and be resynthesized into acetylcholine (ACh).

Figure 7.28 The action of acetylcholinesterase (AChE). The AChE in the postsynaptic cell membrane inactivates the ACh
released into the synaptic cleft. This prevents continued stimulation of the postsynaptic cell unless more ACh is released by the axon.
The acetate and choline are taken back into the presynaptic axon and used to resynthesize acetylcholine.

Presynaptic axon

Presynaptic axon

Postsynaptic cell

Acetylcholinesterase

Acetylcholine

Receptor

Postsynaptic

cell

Acetate

Choline

CLINICAL APPLICATION

Cholinesterase inhibitors are drugs that block the action of

acetylcholinesterase (AChE), thereby increasing the amount

of ACh in the synaptic cleft and enhancing cholinergic synap-

tic transmission. Neostigmine (see table 7.5 ), physostigmine,

pyridostigmine, and others are used to treat myasthenia

gravis, as previously described, and are important in the

treatment of Alzheimer’s disease. However, nerve gas and

organophosphate pesticides can kill their intended victims

by inhibiting AChE and overstimulating cholinergic synapses.

Clinical Investigation CLUES

Denise was careful to eat only produce that did not

contain pesticides.

• If it had organophosphate pesticides, what danger
  might that present?


• Is it likely that pesticides on her restaurant’s
  vegetables would have produced her symptoms?