Gastrointestinal Hormones
TABLE 12-1
S elected P ep tid e C a n d id a te H o rm o n es o f th e G u t
Mechanism of Release and Putative Function
Intestinal mucosa
Mechanism of release unknown; stimulates gastric and pancreatic
secretions directly and by release of gastrin and CCK, respectively;
inhibits absorption of water, Na+, and CI_ from the jejunum.
Mucosa of duodenal bulb
Released by acid; inhibits gastric secretion.
Duodenal mucosa
Functions like glucagon (Chapter 22).
Duodenum and jejunum
Released by vagal stimulation and passage of nutrients; modulates
interdigestive motility, clearing the intestine between meals and
preparing it for another nutritional bolus.
Intestinal mucosa,
pancreas and nerves;
Mechanism of release not clear; multiple inhibitory actions.
Substance P
GI tract (highest
concentrations in small
intestine and colon)
Released after food ingestion, contraction of intestinal smooth
muscle and gall bladder, reduction of bile flow, and increase
in pancreatic juice output.
GI tract (all layers and
Mechanism of release not clear; inhibits gastric acid and pepsin
nerve fibers)
secretion, potent stimulator of intestinal secretion, vasodilator,
possibly neurotransmitter.
*A number of these peptides are found in the gut (in both enteroendocrine cells and enteric neurons) and brain.
secretin ,
ch o lecysto k in in
g astrin ,
g a stric in h ib ito ry p ep tid e.
The hormonal status of
other peptides (sometimes referred to as candidate hor-
mones, Table 12-1) is not yet established. On the ba-
sis of structural similarity, these hormones fall into two
1. The gastrin family, which consists of
gastrin, CCK,
cerulein, enkephalin,
. the secretin family, which consists of
glucagon, vasoactive intestinal peptide
inhibitory peptide
(GIP), and
Other candidate hormones (e.g., neurotensin, substance
P, and somatostatin) belong to neither family. Somato-
statin, considered a candidate hormone in the GI tract, is
an authentic hypothalamic hormone (Chapter 31).
The amino acid sequences of some members of the
gastrin and secretin families are shown in Tables 12-2
and 12-3, respectively. The hormones exhibit both macro-
and microheterogeneity. For example, gastrin exists in
many forms, probably including the principal hormone,
biosynthetic precursors, and metabolites. The sulfate
group on tyrosine at position
1 2
of gastrin may be
missing without significant change in biological activity.
The biological activity of gastrin and CCK resides
in the carboxyterminal tetrapeptide and heptapeptide,
Gastrin is synthesized and stored in G cells in the antral
mucosa of the stomach; it is also found, to a lesser ex-
tent, in the mucosa of the duodenum and jejunum. Dur-
ing fetal life, gastrin is also found in the pancreatic
islet cells. Gastrin-secreting tumors, known as
g a strin o -
m as
(e.g., Zollinger-Ellison syndrome), may develop in
the pancreas. The main form of gastrin obtained from
G cells is a heptadecapeptide. At the N-terminal end of
the heptadecapeptide., there is a pyroglutamyl residue,
and at the C-terminal end, there is a phenylalaninamide
residue, both of which protect the peptide from amino
and carboxy-peptidase activity, respectively. Two forms
of the heptadecapeptide exist: one in which the tyrosyl
residue at position
1 2
is free (gastrin
) and the other
in which it is sulfated (gastrin 2). Though larger and
smaller forms of gastrin have been identified, the biolog-
ical activity of gastrin resides in the C-terminal tetrapep-
tide. A synthetic pentapeptide is available (pentagastrin,
Table 12-2).
Gastrin is released in response to chemical, mechani-
cal, or neural stimuli on the G cell. Hypoglycemia (plasma
glucose concentration C40 mg/dL), acting through the
hypothalamus, causes release of gastrin mediated through
the vagus nerve. A rise in calcium ion concentration in
plasma causes the release of gastrin. The main physiolog-
ical actions of gastrin are stimulation of acid secretion by
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