Ganong's Review of Medical Physiology, 23rd Edition

50 SECTION ICellular & Molecular Basis of Medical Physiology

INTERCELLULAR COMMUNICATION

Cells communicate with one another via chemical messen-
gers. Within a given tissue, some messengers move from cell
to cell via gap junctions without entering the ECF. In addition,
cells are affected by chemical messengers secreted into the
ECF, or by direct cell–cell contacts. Chemical messengers typ-
ically bind to protein receptors on the surface of the cell or, in
some instances, in the cytoplasm or the nucleus, triggering se-
quences of intracellular changes that produce their physiolog-
ic effects. Three general types of intercellular communication
are mediated by messengers in the ECF: (1) neural communi-
cation, in which neurotransmitters are released at synaptic
junctions from nerve cells and act across a narrow synaptic
cleft on a postsynaptic cell; (2) endocrine communication, in
which hormones and growth factors reach cells via the circu-
lating blood or the lymph; and (3) paracrine communication,
in which the products of cells diffuse in the ECF to affect
neighboring cells that may be some distance away (Figure 2–20).
In addition, cells secrete chemical messengers that in some sit-
uations bind to receptors on the same cell, that is, the cell that
secreted the messenger (autocrine communication). The
chemical messengers include amines, amino acids, steroids,
polypeptides, and in some instances, lipids, purine nucleo-
tides, and pyrimidine nucleotides. It is worth noting that in
various parts of the body, the same chemical messenger can
function as a neurotransmitter, a paracrine mediator, a hor-
mone secreted by neurons into the blood (neural hormone),
and a hormone secreted by gland cells into the blood.
An additional form of intercellular communication is called
juxtacrine communication. Some cells express multiple
repeats of growth factors such as transforming growth factor
alpha (TGFα) extracellularly on transmembrane proteins
that provide an anchor to the cell. Other cells have TGFα
receptors. Consequently, TGFα anchored to a cell can bind to
a TGFα receptor on another cell, linking the two. This could
be important in producing local foci of growth in tissues.

RECEPTORS FOR

CHEMICAL MESSENGERS

The recognition of chemical messengers by cells typically be-

gins by interaction with a receptor at that cell. There have been

over 20 families of receptors for chemical messengers charac-

terized. These proteins are not static components of the cell,

but their numbers increase and decrease in response to vari-

ous stimuli, and their properties change with changes in phys-

iological conditions. When a hormone or neurotransmitter is

present in excess, the number of active receptors generally de-

creases (down-regulation), whereas in the presence of a defi-

ciency of the chemical messenger, there is an increase in the

number of active receptors (up-regulation). In its actions on

the adrenal cortex, angiotensin II is an exception; it increases

rather than decreases the number of its receptors in the adre-

nal. In the case of receptors in the membrane, receptor-medi-

ated endocytosis is responsible for down-regulation in some

instances; ligands bind to their receptors, and the ligand–

receptor complexes move laterally in the membrane to coated

pits, where they are taken into the cell by endocytosis (inter-

nalization). This decreases the number of receptors in the

membrane. Some receptors are recycled after internalization,

whereas others are replaced by de novo synthesis in the cell.

Another type of down-regulation is desensitization, in which

receptors are chemically modified in ways that make them less

responsive.

MECHANISMS BY WHICH

CHEMICAL MESSENGERS ACT

Receptor–ligand interaction is usually just the beginning of the

cell response. This event is transduced into secondary responses

within the cell that can be divided into four broad categories:

(1) ion channel activation, (2) G-protein activation, (3) activa-

tion of enzyme activity within the cell, or (4) direct activation of

transcription. Within each of these groups, responses can be

quite varied. Some of the common mechanisms by which

FIGURE 2–20 Intercellular communication by chemical mediators. A, autocrine; P, paracrine.

A P

ENDOCRINE

Message transmission

Local or general

Specificity depends on Anatomic location

Local Local

Anatomic location

and receptors

GAP JUNCTIONS SYNAPTIC

PARACRINE AND

AUTOCRINE

By circulating

body fluids

General

Receptors Receptors

Locally diffuse

By diffusion in

interstitial fluid

Across synaptic

cleft

Directly from cell

to cell