Ulceration and erosion of the lining of the gastrointestinal
tract are common problems. Mucosal erosions or ulcerations arise
when the caustic effects of pepsin, acid, or bile overwhelm the
defensive factors such as mucus, prostaglandins, and bicarbonate.
Cells lining the stomach include mucus-producing cells, parietal
cells, and gastrin-containing cells. Parietal cells contain receptors for
gastrin, histamine, and acetylcholine (Figure 36–3). When
ACh or gastrin bind to parietal cell receptors, they cause an increase
in cytosolic calcium, which in turn activates protein kinases that stimulate
acid secretion from a H+/K+–ATPase
(proton pump) on the canalicular surface. This proton pump exchanges
intracellular H+ for K+ present
in the lumen of the stomach. In close proximity to the parietal
cells are gut endocrine cells called enterochromaffin-like cells.
These cells have receptors for gastrin, ACh, and neuropeptides,
and are the major source for histamine release. Histamine binds
to the H2 receptor on the parietal cell, resulting in activation
of adenylyl cyclase, which increases intracellular cyclic adenosine
monophosphate (cAMP). The cAMP activates protein kinases that stimulate
H+ secretion by the proton pump. Research suggests that
the major effect of gastrin upon acid secretion is mediated indirectly
through the release of histamine rather than through direct parietal cell
stimulation.