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Background: Gastrin regulates gastric acid secretion and gastric mucosal cell proliferation. We hypothesized that pentagastrin administration would affect mRNA levels of two membrane proteins that are important during stimulated states of HCl secretion, the basolateral Na-K-Cl cotransporter (BSC) and the apical H/K adenosine triphosphatase (H/K)., Methods: Two groups of Fischer rats received intraperitoneal injections of pentagastrin (2.5 or 25 micrograms/kg) every 8 hours for three doses. A third group served as controls. An additional group received pentagastrin plus the gastrin receptor antagonist (GRA) L740,093. Fundic mucosae were subjected to semiquantitative Northern analysis of mRNAs encoding H/K and BSC. The mRNA for Na/K adenosine triphosphatase (Na/K), a transport protein not involved directly in acid secretion, also was evaluated., Results: Administration of pentagastrin caused dose-dependent increases in levels of mRNAs encoding H/K and BSC but had no significant effect on levels of Na/K mRNA. Administration of GRA prevented the pentagastrin-induced changes in mRNA levels for these transporters., Conclusions: Pentagastrin administration selectively up-regulates levels of mRNA encoding membrane proteins involved in acid secretion. The up-regulation of the mRNAs encoding BSC during pentagastrin stimulation indicates that regulation of basolateral Cl- movement may be as important as the regulation of apical H+ movement under stimulated states.

Acute gastric mucosal injury and bleeding occur in the settings of both respiratory acidosis or metabolic acidosis secondary to systemic sepsis or shock. Respiratory acidosis, however, is more predictably associated with acute injury than metabolic acidosis. We hypothesized that the gastric surface epithelial cells are more susceptible to acute increases in PCO2 than to acute decreases in HCO3-, even for the same level of extracellular acidification. To evaluate this hypothesis, we used intracellular microelectrodes to measure pHi, cell membrane potential (Vc), as well as ion conductances of the apical (Ga) and basolateral (Gb) membranes and the paracellular pathway (Gs) in gastric mucosal cells during acute changes in serosal PCO2 or HCO3-. Necturus antral mucosae were mounted in Ussing chambers, perfused on both sides by Ringer solution (40 mmHg PCO2, 18 mM HCO3-, pH 7.3). Measurements were performed before and during increases in PCO2 (80 mmHg, pH 7.0) or decreases in HCO3- (7.2 mM, pH 6.8 or 2.4 mM, pH 6.4). Both forms of acidosis acidified pHi, depolarized membrane potentials, and decreased ion conductances across apical and basolateral membranes, but not the paracellular pathways. For the same level of extracellular acidification, increases in PCO2 were more effective than acute decreases in HCO3- in acidifying pHi and eliciting disturbances in voltage-generating and ion permeability properties of the cell membranes. These findings suggest that pH-buffering mechanisms in gastric surface cells respond less effectively to high PCO2 than low HCO3.