Ganong's Review of Medical Physiology, 23rd Edition

434
SECTION V
Gastrointestinal Physiology

is terminated after the meal moves from the stomach into the
small intestine.
Gastric parietal cells are highly specialized for their unusual
task of secreting concentrated acid (Figure 26–8). The cells are
packed with mitochondria that supply energy to drive the api-
cal H,K-ATPase, or proton pump, that moves H

• ions out of the
  parietal cell against a concentration gradient of more than a

million-fold. At rest, the proton pumps are sequestered within

the parietal cell in a series of membrane compartments known

as tubulovesicles. When the parietal cell begins to secrete, on

the other hand, these vesicles fuse with invaginations of the api-

cal membrane known as canaliculi, thereby substantially ampli-

fying the apical membrane area and positioning the proton

pumps to begin acid secretion (Figure 26–9). The apical mem-

brane also contains potassium channels, which supply the K

+

ions to be exchanged for H

+

, and Cl

• channels that supply the
  counterion for HCl secretion (Figure 26–10). The secretion of
  protons is also accompanied by the release of equivalent num-
  bers of bicarbonate ions into the bloodstream, which as we will
  see, are later used to neutralize gastric acidity once its function
  is complete (Figure 26–10).
  The three agonists of the parietal cell—gastrin, histamine,
  and acetylcholine—each bind to distinct receptors on the
  basolateral membrane (Figure 26–9). Gastrin and acetylcho-
  line promote secretion by elevating cytosolic free calcium con-
  centrations, whereas histamine increases intracellular cyclic
  adenosine 3',5'-monophosphate (cAMP). The net effect of
  these second messengers are the transport and morphological
  changes described above. However, it is important to be aware
  that the two distinct pathways for activation are synergistic,
  with a greater than additive effect on secretion rates when his-
  tamine plus gastrin or acetylcholine, or all three, are present
  simultaneously. The physiologic significance of this synergism
  is that high rates of secretion can be stimulated with relatively
  small changes in availability of each of the stimuli. Synergism
  is also therapeutically significant because secretion can be
  markedly inhibited by blocking the action of only one of the
  triggers (most commonly that of histamine, via H
  2
  histamine
  antagonists that are widely used therapies for adverse effects of
  excessive gastric secretion, such as reflux).

FIGURE 26–6
Cyanocobalamin (vitamin B
12
).

N

N

O

H

H HH

HO CH 2

CH 3

O HO CH 3

P

O

O O

CHCH 2 NH

CH 3 CO

CH 2

CH 2

CH 3

CH 3

CH 3

CH 3

CH 3

CH 3

−

+

C

C

Co

CN

CH 2 CH 2 CONH 2

NH 2 COCH 2

CH 2 CH 2 CONH 2

N N

CH

N

B

C

A

D

N

CH 2 CONH 2

CH 2 CH 2 CONH 2

NH 2 COCH 2

H 3 C

H 3 C

FIGURE 26–7
Regulation of gastric acid and pepsin secretion by soluble mediators and neural input.
Gastrin is released from G cells in the
antrum and travels through the circulation to influence the activity of ECL cells and parietal cells. The specific agonists of the chief cell are not well under-
stood. Gastrin release is negatively regulated by luminal acidity via the release of somatostatin from antral D cells.
(Adapted from Barrett KE:
Gastrointestinal
Physiology

. McGraw-Hill, 2006.)

−

G cell

GRP

ANTRUM

Peptides/amino acids

D cell

SST

Gastrin

H+

Nerve ending

Circulation ECL cell

Histamine

ACh??

ACh

P

Chief cell

Parietal cell

ACh

H+

FUNDUS