256 Chapter 9
to diffuse inward and K^1 to diffuse outward. However, the Na^1
gradient is steeper than the K^1 gradient, and so the net effect is
a depolarization. As a result, nicotinic ACh receptors are always
excitatory. In contrast, muscarinic ACh receptors are coupled to
G-proteins, which can then close or open different membrane
channels and activate different membrane enzymes. As a result,
their effects can be either excitatory or inhibitory ( fig. 9.11 ).
Scientists have identified five different subtypes of musca-
rinic receptors (M 1 through M 5 ; table 9.6 ). Some of these cause
contraction of smooth muscles and secretion of glands, while
others cause the inhibition that results in a slowing of the heart
rate. These actions are mediated by second-messenger systems
that will be discussed in more detail in conjunction with hor-
mone action in chapter 11, section 11.2.Responses to Cholinergic Stimulation
All somatic motor neurons, all preganglionic neurons (sympa-
thetic and parasympathetic), and most postganglionic parasym-
pathetic neurons are cholinergic—they release acetylcholine
(ACh) as a neurotransmitter. The effects of ACh released by
somatic motor neurons and by preganglionic autonomic neurons
are always excitatory. The effects of ACh released by postgangli-
onic parasympathetic axons are usually excitatory, but in some
cases they are inhibitory. For example, the cholinergic effect of
the postganglionic parasympathetic axons innervating the heart
(a part of the vagus nerve) slows the heart rate. It is useful to
remember that, in general, the effects of parasympathetic inner-
vation are opposite to the effects of sympathetic innervation.
The effects of ACh in an organ depend on the nature of the
cholinergic receptor ( fig. 9.11 ). As may be recalled from chap-
ter 7, there are two types of cholinergic receptors—nicotinic
and muscarinic. Nicotine (derived from the tobacco plant), as
well as ACh, stimulates the nicotinic ACh receptors. These are
located in the CNS, neuromuscular junction of skeletal muscle
fibers, and in the autonomic ganglia. Nicotinic receptors are
thus stimulated by ACh released by somatic motor neurons and
by preganglionic autonomic neurons. Muscarine (derived from
some poisonous mushrooms), as well as ACh, stimulates the
ACh receptors in the visceral organs. Muscarinic receptors are
thus stimulated by ACh released by postganglionic parasympa-
thetic axons to produce the parasympathetic effects. Nicotinic
and muscarinic receptors are further distinguished by the action
of the drugs curare (tubocurarine), which specifically blocks
the nicotinic ACh receptors, and atropine (or belladonna ),
which specifically blocks the muscarinic ACh receptors.
As described in chapter 7, the nicotinic ACh receptors are
ligand-gated ion channels. That is, binding to ACh causes the
ion channel to open within the receptor protein. This allows Na^1
Receptor Types Drugs That Stimulate Drugs That Block
a 1 -Adrenergic Phenylephrine (vasoconstrictor; nasal decongestant) Phentolamine (short-term control of hypertension)
a 2 -Adrenergic Clonidine (control of hypertension) Yohimbine (raises blood pressure; improved male sexual
function)
b 1 -Adrenergic Dobutamine (increased cardiac contractility and
cardiac output)Metoprolol; atenolol (treatment of hypertension)b 2 -Adrenergic Terbutaline; albuterol (dilate bronchioles to treat
asthma)
Muscarinic
cholinergicMethacholine; pilocarpine (pilocarpine used to
constrict pupils)Atropine (reduces secretions of respiratory passages; treats
overactive bladder; reduces intestinal contractions;
others)
Nicotinic cholinergic Nicotine (no therapeutic uses; numerous toxic
effects include first stimulation then depression
of all autonomic ganglia and neuromuscular
junctionsD-tubocurarine (neuromuscular blockade causing muscle
relaxation during surgery and orthopedic procedures)Table 9.5 | Examples of Adrenergic and Cholinergic Agonists and Antagonists
Selected therapeutic uses of these drugs are given in parentheses.
Modified from table 6-9, pp. 171–172, of Goodman and Gilman’s The Pharmacological Basis of Therapeutics. Eleventh edition. 2006. McGraw-Hill.
CLINICAL APPLICATION
Atropine, from the deadly nightshade plant ( Atropa bel-
ladonna ), is a specific antagonist of the muscarinic ACh
receptors, and thus of the effects of postganglionic para-
sympathetic axons. It is infused on the eyes to inhibit the
muscle contraction that constricts the pupils (chapter 10; see
fig. 10.28), resulting in pupil dilation for eye exams. Women
during the Middle Ages used this effect to make their eyes
more attractive (in Italian, bella 5 beautiful, donna 5 woman).
In addition, atropine can be used to block the vagus nerve–
induced slowing of the heart, helping to treat bradycardia (a
slow heart rate) and AV node heart block. Atropine is used
to reduce the production of saliva and mucus (sometimes
before general anesthesia), and to inhibit spasmodic con-
tractions of the intestine and the stomach acid secretion of
gastritis. Atropine is also used as a treatment for nerve gas
and organophosphate pesticide poisoning, because these
compounds can inhibit acetylcholinesterase (AChE) to dan-
gerously increase cholinergic transmission.