Human Physiology, 14th edition (2016)

254 Chapter 9

binds to the a 1 receptors is mediated by a different second-

messenger system—a rise in the cytoplasmic concentration

of Ca^2 1. This Ca^2 1 second-messenger system is similar, in

many ways, to the cAMP system and is discussed together

with endocrine regulation in chapter 11 (see fig. 11.10). It

should be remembered that each of the intracellular changes

following the binding of norepinephrine to its receptor ulti-

mately results in the characteristic response of the tissue to

the neurotransmitter.

There are different subtypes of a 2 -adrenergic receptors

that produce different effects. The a 2 -adrenergic receptors

located on presynaptic axon terminals produce a decreased

release of norepinephrine when activated by norepinephrine

in the synaptic cleft. This provides negative feedback control

over the amount of norepinephrine released. The most medi-

cally important subtype of a 2 -adrenergic receptors is located

in the brain. When these receptors are stimulated by the drug

clonidine, they produce a lowering of blood pressure by some-

how reducing the activation of the entire sympathoadrenal

system.

A review of table  9.4 reveals certain generalities about

the actions of adrenergic receptors. The stimulation of a 1 -

adrenergic receptors consistently causes contraction of smooth

muscles. We can thus state that the vasoconstrictor effect of

sympathetic nerves always results from the activation of alpha-

adrenergic receptors. The effects of beta-adrenergic activation

are more diverse; stimulation of beta-adrenergic receptors pro-

motes the relaxation of smooth muscles (in the digestive tract,

bronchioles, and uterus, for example) but increases the force

of contraction of cardiac muscle and promotes an increase in

cardiac rate.

The diverse effects of epinephrine and norepinephrine can

be understood in terms of the “fight-or-flight” theme. Norepi-

nephrine released by postganglionic sympathetic axons, and

epinephrine released into the blood from the adrenal medulla,

boost the ability of the cardiovascular system to respond to

physical emergencies. The a -adrenergic receptors are more

sensitive to norepinephrine, whereas the b -adrenergic recep-

tors are more sensitive to epinephrine circulating in the blood.

Stimulation of b 1 - and b 2 -adrenergic receptors in the heart

increases heart rate and contractility. In the arterioles (small

arteries) of the body, a 1 -adrenergic receptors stimulate vaso-

constriction and b 2 -adrenergic receptors promote vasodilation

in appropriate organs to prepare the body for physical exertion

( fig. 9.10 ).

A drug that binds to the receptors for a neurotransmitter

and that promotes the processes that are stimulated by that

neurotransmitter is said to be an agonist of that neurotrans-

mitter. A drug that blocks the action of a neurotransmitter, by

contrast, is said to be an antagonist. The use of specific drugs

that selectively stimulate or block a 1 ,  a 2 ,  b 1 , and b 2 receptors

has proven extremely useful in many medical applications.

Examples of drugs that stimulate (as agonists) and block (as

antagonists) adrenergic and cholinergic receptors are provided

in table 9.5.

recently discovered b 3 -adrenergic receptor located primarily
in adipose tissue, which promotes lipolysis and heat produc-
tion.) Compounds have been developed that selectively bind
to one or the other type of adrenergic receptor and, by this
means, either promote or inhibit the normal action produced
when epinephrine or norepinephrine binds to the receptor. As
a result of its binding to an adrenergic receptor, a drug may
either promote or inhibit the adrenergic effect. Also, by using
these selective compounds, it has been possible to determine
which subtype of adrenergic receptor is present in each organ
( table 9.4 ).
All adrenergic receptors act via G-proteins. The action of
G-proteins was described in chapter 7, and can be reviewed by
reference to figure 7.27 and table 7.6. In short, the binding of
epinephrine and norepinephrine to their receptors causes the
group of three G-proteins (designated a ,  b , and g ) to dissociate
into an a subunit and a b g complex. In different cases, either
the a subunit or the b g complex causes the opening or closing
of an ion channel in the plasma membrane, or the activation
of an enzyme in the membrane. This begins the sequence of
events that culminates in the effects of epinephrine and norepi-
nephrine on the target cells.
All subtypes of beta receptors produce their effects by
stimulating the production of cyclic AMP within the target
cells. The response of a target cell when norepinephrine

Organ

Adrenergic Effects

of Sympathoadrenal

System

Adrenergic

Receptor

Eye Contraction of radial fibers of

the iris dilates the pupils

a 1

Heart Increase in heart rate and

contraction strength

b 1 primarily

Skin and

visceral

vessels

Arterioles constrict due to

smooth muscle contraction

a 1

Skeletal

muscle

vessels

Arterioles constrict due to

sympathetic nerve activity

a 1

Arterioles dilate due to

hormone epinephrine

b 2

Lungs Bronchioles (airways) dilate due

to smooth muscle relaxation

b 2

Stomach and

intestine

Contraction of sphincters slows

passage of food

a 1

Liver Glycogenolysis and secretion

of glucose

a 1 ,  b 2

Table 9.4 | Selected Adrenergic Effects
in Different Organs

Source: Simplified from table 6-1, pp. 143–144, of Goodman and Gilman’s
The Pharmacological Basis of Therapeutics. Eleventh edition. J.E. Hardman
et al., eds. 2006. McGraw-Hill.