206
chapter
12
Gastrointestinal Digestion and Absorption
HCI
B a solateral m em b ran e
F IG U R E 12-3
Schematic representation of the resting (left side) and stimulated (right
side) state of the parietal cell. Basolateral membrane contains three major
receptor classes: gastrin (G), acetylcholine (ACh), and histamine (H). Their
actions are mediated by cAMP responses, Ca2+ changes, or both. In
addition, there are a number of ion transport pathways. In the stimulated
state, the apical membrane acquires H+,K+-ATPase contained in the
tubulovesicles (tv) as well as the property of K+ and Cl- conductance, both
of which are essential in the secretion of HCI. A change in cytoskeletal
arrangement is also associated with stimulation. CaM = calmodulin; SC =
secretory canaliculus; mf = microfilaments. [Reproduced with permission
from D. H. Malinowska and G. Sachs, Cellular mechanisms of acid
secretion,
C lin. G a stro en tero l.
13,
322 (1984).]
r
<
.c h
2
c h , n h ,+
HN
N
H istam in e
H3C
C H
2
SC H ,C H ,N H C N H C H
3
> = <
II
HN
N
N
C — N
x .
^
C im etid in e
/ ‘N
H3C
C H
3
F IG U R E 1 2 -4
Comparison of the structures of histamine with cimetidine and ranitidine.
The latter two are H
2
-receptor antagonists and act on the gastric parietal
cells to inhibit gastric acid production. Ranitidine, which has a furan rather
than an imidazole structure, is a more potent competitive inhibitor than
cimetidine.
OMEPRAZOLE
H+
SULFENAMIDE
SULFENIC ACID
<
Q
OCH,
ENZYME-INHIBITOR COMPLEX
FIGURE 12-5
Inhibition of H+,K+-ATPase by omeprazole. In the acidic pH of the
stomach, omeprazole is converted to sulfenamide, which forms an
enzyme-inhibitor complex by disulfide linkage.
transfer of an HC0
3
into the plasma in exchange for Cl- ,
which is ultimately secreted into the gastric lumen. In
instances of excessive loss of gastric fluids (e.g., persistent
vomiting or nasogastric suction), metabolic alkalosis re-
sults (Chapter 39).
