448 SECTION V Gastrointestinal Physiology
pancreatic exocrine secretion; gastric acid secretion and motili-
ty; gallbladder contraction; and the absorption of glucose, ami-
no acids, and triglycerides.
OTHER GASTROINTESTINAL
PEPTIDES
PEPTIDE YY
The structure of peptide YY is discussed in Chapter 21. It also
inhibits gastric acid secretion and motility and is a good can-
didate to be the gastric inhibitory peptide (Figure 26–23). Its
release from the jejunum is stimulated by fat.
OTHERS
Ghrelin is secreted primarily by the stomach and appears to
play an important role in the central control of food intake. It
also stimulates growth hormone secretion by acting directly
on receptors in the pituitary (see Chapter 24).
Substance P (Table 26–6) is found in endocrine and nerve
cells in the gastrointestinal tract and may enter the circulation.
It increases the motility of the small intestine. The neurotrans-
mitter GRP contains 27 amino acid residues, and the 10 amino
acid residues at its carboxyl terminal are almost identical to
those of amphibian bombesin. It is present in the vagal nerve
endings that terminate on G cells and is the neurotransmitter
producing vagally mediated increases in gastrin secretion. Glu-
cagon from the gastrointestinal tract may be responsible (at
least in part) for the hyperglycemia seen after pancreatectomy.
Guanylin is a gastrointestinal polypeptide that binds to gua-
nylyl cyclase. It is made up of 15 amino acid residues (Table
26–6) and is secreted by cells of the intestinal mucosa. Stimula-
tion of guanylyl cyclase increases the concentration of intracell-
ular cyclic 3',5'-guanosine monophosphate (cGMP), and this in
turn causes increased secretion of Cl– into the intestinal lumen.
Guanylin appears to act predominantly in a paracrine fashion,
and it is produced in cells from the pylorus to the rectum. In an
interesting example of molecular mimicry, the heat-stable
enterotoxin of certain diarrhea-producing strains of E. coli has a
structure very similar to guanylin and activates guanylin recep-
tors in the intestine. Guanylin receptors are also found in the
kidneys, the liver, and the female reproductive tract, and guany-
lin may act in an endocrine fashion to regulate fluid movement
in these tissues as well, and particularly to integrate the actions
of the intestine and kidneys.
THE ENTERIC NERVOUS SYSTEM
Two major networks of nerve fibers are intrinsic to the gas-
trointestinal tract: the myenteric plexus (Auerbach’s plexus),
between the outer longitudinal and middle circular muscle lay-
ers, and the submucous plexus (Meissner’s plexus), between
the middle circular layer and the mucosa (Figure 26–1). Collec-
tively, these neurons constitute the enteric nervous system.
The system contains about 100 million sensory neurons, inter-
neurons, and motor neurons in humans—as many as are found
in the whole spinal cord—and the system is probably best
viewed as a displaced part of the central nervous system (CNS)
that is concerned with the regulation of gastrointestinal func-
tion. It is sometimes referred to as the “little brain” for this rea-
son. It is connected to the CNS by parasympathetic and
sympathetic fibers but can function autonomously without
these connections (see below). The myenteric plexus innervates
the longitudinal and circular smooth muscle layers and is con-
cerned primarily with motor control, whereas the submucous
plexus innervates the glandular epithelium, intestinal endocrine
cells, and submucosal blood vessels and is primarily involved in
the control of intestinal secretion. The neurotransmitters in the
system include acetylcholine, the amines norepinephrine and
serotonin, the amino acid γ-aminobutyrate (GABA), the purine
adenosine triphosphate (ATP), the gases NO and CO, and
many different peptides and polypeptides (Table 26–8). Some
of these peptides also act in a paracrine fashion, and some enter
the bloodstream, becoming hormones. Not surprisingly, most
of them are also found in the brain.EXTRINSIC INNERVATION
The intestine receives a dual extrinsic innervation from the au-
tonomic nervous system, with parasympathetic cholinergic ac-
tivity generally increasing the activity of intestinal smoothTABLE 26–8 Principal peptides found in the enteric
nervous system.CGRP
CCK
Endothelin-2
Enkephalins
Galanin
GRP
Neuropeptide Y
Neurotensin
Peptide YY
PACAP
Somatostatin
Substance P
TRH
VIP