Chapter 1
once given the appropriate stimulus, into the extracellular
fl uid. They then diffuse to neighboring cells, some of which
are their target cells. Note that, given this broad defi ni-
tion, neurotransmitters could be classifi
ed as a subgroup of
paracrine agents, but by convention they are not. Paracrine
agents are generally inactivated rapidly by locally existing
enzymes so that they do not enter the bloodstream in large
There is one category of local chemical messengers that
are not
cellular messengers—that is, they do not com-
cells. Rather, the chemical is secreted by a
cell into the extracellular fl uid and then acts upon the very
cell that secreted it. Such messengers are termed
(see Figure 1–8). Frequently a messenger may serve
both paracrine and autocrine functions simultaneously—that
is, molecules of the messenger released by a cell may act locally
on adjacent cells as well as on the same cell that released the
One of the most exciting developments in physiology
today is the identifi cation of a growing number of paracrine/
autocrine agents and the extremely diverse effects they exert.
Their structures range from a simple gas such as nitric oxide
to fatty acid derivatives such as the eicosanoids (Chapter 5), to
peptides and amino acid derivatives. They tend to be secreted
by multiple cell types in many tissues and organs. According
to their structures and functions, they can be classifi ed into
families. For example, one such family constitutes the growth
factors, encompassing more than 50 distinct molecules, each
of which is highly effective in stimulating certain cells to
divide and/or differentiate.
Stimuli for the release of paracrine/autocrine agents
are also extremely varied. These include not only local chem-
ical changes, such as in the concentration of oxygen, but
neurotransmitters and hormones as well. In these two latter
cases, the paracrine/autocrine agent often serves to oppose
the effects the neurotransmitter or hormone induces locally.
For example, the neurotransmitter norepinephrine strongly
constricts blood vessels in the kidneys, but it simultaneously
causes certain kidney cells to secrete paracrine agents that
cause the same vessels to dilate. This provides a local nega-
tive feedback, in which the paracrine agents keep the action
of norepinephrine from becoming too intense. This, then,
is an example of homeostasis occurring at a highly localized
A point of great importance must be emphasized here to
avoid later confusion. A nerve cell, endocrine gland cell, and
other cell type may all secrete the same chemical messenger.
Thus, a particular messenger may sometimes function as a
neurotransmitter, as a hormone, or as a paracrine/autocrine
agent. Norepinephrine, for example, is not only a neurotrans-
mitter in the brain, it is also produced as a hormone by cells of
the adrenal glands.
All types of intercellular communication described so far
in this section involve secretion of a chemical messenger into
the extracellular fl uid. However, there are two important types
of chemical communication between cells that do not require
such secretion. In the fi rst type, which occurs via gap junc-
tions (Chapter 3), molecules move from one cell to an adja-
cent cell without ever entering the extracellular fl
uid. In the
second type, the chemical messenger is not actually released
from the cell producing it but rather is located in the plasma
membrane of that cell. When the cell encounters another cell
type capable of responding to the message, the two cells link
up via the membrane-bound messenger. This type of signal-
ing, sometimes termed “juxtacrine”, is of particular impor-
tance in the growth and differentiation of tissues as well as in
the functioning of cells that protect the body against microbes
and other foreign agents (Chapter 18).
Target cell
gland cell
Nerve cell
Local cell
Local cell
Paracrine agent
Autocrine agent
Target cell
Neuron or
effector cell
Figure 1–8
Categories of chemical messengers. With the exception of autocrine agents, all messengers act between cells—that is,
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