204
chapter
12
Gastrointestinal Digestion and Absorption
TABLE 12-2
P rim a ry S tru ctu re o f G astrin F am ily
*
Hormone
Molecular Weight
Structure
Gastrin^
Big gastrin
(G-34)
3839
PyL-Leu-
Gly-Pro-Gln-Gly-His-Pro-Ser-Leu-Val-
Ala-Asp-Pro-Ser-Lys-Lys-Gln-Gly-Pro-
Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH
2
Little gastrin
(G-17)
2098
Pyr^-Gly-Pro-
Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH
2
Minigastrin
(G-14)
1833
Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH
2
Pentagastrin
768
N-t-butyloxycarbonyl-/3-Ala-Trp-Met-Asp-Phe-NH
2
Cholecystokinin®
CCK-39
4678
Tyr-Ile-Gln-Gln-Ala-Arg-Lys-
Ala-Pro-Ser-Gly-Arg-Val-Ser-Met-Ile-
Lys-Asn-Leu-Gln-Ser-Leu-Asp-Pro-Ser-
His-Arg-Ile-Ser-Asp-Arg-Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH
2
CCK-33
3918
Lys-
Ala-Pro-Ser-Gly-Arg-Val-Ser-Met-Ile-
Lys-Asn-Leu-Gln-Ser-Leu-Asp-Pro-Ser-
His-Arg-Ile-Ser-Asp-Arg-Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH
2
CCK
- 8
1143
Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH
2
CCK-4
597
Trp-Met-Asp-Phe-NH
2
Caerulein
1352
Asp-Arg-Asp-Tyr-Met-Gly-Trp-Met-Asp-Phe-NH
2
♦Reproduced, with permission, from J. C. Thompson and M. Marx: Gastrointestinal hormones.
C urr. P ro b l. S u rg .,
21(6), 19 (1984). © 1984 by Year
Book Medical Publishers.
I’Human.
tPyr, glutamine in pyriform.
^Porcine.
parietal cells, secretion of pepsin by chief cells, increase in
gastric mucosal blood flow, stimulation of gastric motility,
and promotion of the growth of oxyntic mucosa and ex-
ocrine pancreatic tissue. Release of gastrin is suppressed
by acidification of the antral mucosa. In disorders in which
H+ is not excreted owing to destruction or absence of
functioning parietal cells (e.g.,
p e rn ic io u s a n em ia , a t-
ro p h ic g a stritis
), gastrin plasma levels are highly elevated.
Plasma levels of gastrin are also elevated in the
Z o llin g er—
E lliso n syn d ro m e,
in which hypersecretion of acid, peptic
ulcer disease, and hyperplasia of the gastric mucosa oc-
cur. Gastrin release is suppressed by all members of the
secretin family (Table 12-3).
The mechanism of acid secretion by parietal cells is
complex and not completely understood. These cells have
many receptors and are subjected to a variety of stimuli
that can act independently or modulate one another’s ac-
tion. If intracellular pH is assumed to be 7 and lumi-
nal pH 1, parietal cells secrete H+ at a concentration a
million-fold higher than that inside the cell. Parietal cells
contain the largest number of mitochondria found in eu-
karyotic cells. They are polar: at the apical membrane,
HC1 is secreted into the gastric lumen, and at the ba-
solateral membrane, HCOJ is secreted. The basolateral
membrane contains many different receptors, ion chan-
nels, and transport pathways. The resting cell is packed
with membrane-bound vesicles called tubulovesicles the
membranes of which contain H+, K+-ATPase (a pro-
ton pump), the enzyme responsible for acid secretion.
When the cell is stimulated, these tubulovesicles inter-
act by means of cytoskeletal elements to form a secre-
tory canaliculi. A schematic representation of receptor
