Cell biology of gastric acid secretion

Pituitary Adenylate Cyclase-Activating Polypeptide and Its Receptors: 20 Years after the Discovery

“…Consistent with these observations, the presence of PAC1-R has been detected on gastric ECL cells (Zeng et al, 1999a). Because histamine is a potent stimulator of chloride secretion (Helander and Keeling, 1993), these data suggest that the effect of PACAP on gastric acid production can be accounted for, at least in part, by an indirect stimulation of ECL cells (Sandvik et al, 2001). In support of this hypothesis, PACAP elevates [Ca 2ϩ ] i in ECL cells and adjacent parietal cells in rabbit gastric glands, whereas histamine receptor antagonists abolish the Ca 2ϩ response in adjacent parietal cells (Athmann et al, 2000).…”

Colocalization of KCNQ1/KCNE channel subunits in the mouse gastrointestinal tract

“…This strongly suggests that -in contrast to intestinal crypt cells -KCNQ1 is not expressed in the basolateral membrane of parietal cells, but operates in parallel to the H + /K + -ATPase in the extended system of tubulovesicular and canalicular membranes. Thus, somewhat analogous to the function in intestinal crypt cells, KCNQ1 may serve as a recycling pathway for K + ions that are transported by the H + /K + -ATPase [9,10]. This again raised the question of whether it associates with a β-subunit, prompting us to search for KCNE family members in the stomach.…”

Gastric function and its contribution to the postprandial metabolic response of the Burmese pythonPython molurus

“…Contractions of the stomach's smooth muscles serve to churn and grind the ingested meal, thereby facilitating contact of the food with enzymes and HCl, and to drive chyme through the pyloric sphincter. For non-mammalian species, a single cell type, the oxyntic cell, is responsible for the secretion of pepsinogen and HCl (handled by the chief and parietal cells, respectively, in mammals; Helander and Keeling, 1993). Secreted pepsinogen, when exposed to a luminal pH of 2-3.5, is cleaved to the active proteolytic enzyme pepsin.…”

“…HCl is formed from Cl -and H + ; Clis passively released from oxyntic cells whereas H + is actively pumped from cells by the ATP-driven H + /K + -exchanger (H + /K + -ATPase or proton pump; Forte et al, 1980). While motility and pepsinogen production undoubtedly both contribute to the cost of gastric digestion, at least five lines of evidence emphasize the cost of acid production: (1) pythons maintain an intragastric pH of 1.5 in spite of the large buffering capacity of the rat meals for 5-7·days; (2) the production of such a quantity of HCl requires the proton pumps of the oxyntic cells to move H + from the cytosol into the gastric lumen against a concentration gradient in excess of a million-fold (Helander and Keeling, 1993); (3) the proton pumps operate via the hydrolysis of ATP with a stoichiometry of one H + pumped per ATP hydrolyzed (Reenstra and Forte, 1981;Norberg and Mårdh, 1990); (4) the gastric parietal cells of mammals contain the highest concentration of mitochondria (34-44% by volume) compared with any other mammalian cell type (Helander and Hirschowitz, 1972;Helander et al, 1986), and, in a preliminary study, I found python oxyntic cells to be 40% mitochondria by volume; and (5) acid secretion is absolutely dependent upon oxygen delivery (Forte et al, 1975;Berglindh, 1984). Collectively, these findings indicate that pythons expend considerable amounts of cellular energy via aerobic metabolic pathways to generate the vast quantity of HCl necessary to digest their large intact meals.…”

“…Given that gastric function (i.e. acid and enzyme secretion) is energetically demanding (Reenstra and Forte, 1981;Helander and Keeling, 1993), the gastric breakdown of the python's meal may occur at a relatively high cost (compared with that of other carnivores) and thus explain their comparatively larger SDA.…”