W1542 Effect of Carbon Monoxide On HCO3- Secretion in Rat Stomachs: Involvement of Heme Oxygenase in Regulation of Gastric HCO3- Response

Abstract

G A A b st ra ct s -/mice to wild type mice to determine if zinc works via the receptor or by direct interactions within the cytosol. Material and methods: Wild type and CaSR-deficient mice were fasted for 12-18 hours prior to sacrifice to ensure a consistent minimum of gastric acid secretion. Single gastric glands were hand-dissected from the corpus of the stomach. After incubation with the pH-sensitive dye, BCECF glands were transferred to a coverslip precoated with a biological cell adhesive, mounted in a chamber maintained at 37° and then imaged on a real time fluorescence digital system. For reproducible acidification, glands were exposed to a Na+-free NH4Cl prepulse and a 0 mM Na+ solution. Following acid loading and Na+removal, acid extrusion was monitored as rate of intracellular alkalinization. To examine proton extrusion by H+,K+-ATPase and to preclude contribution of Na+/H+ exchange, Na+free conditions were chosen. The rate of pH recovery, representing H+,K+-ATPase activity, was calculated as ΔpHi/Δt, using a high-K+/Nigericin calibration technique. In wild type mice Histamine or a potent calcimimetic activator of the CaSR, were used to stimulate acid secretion. In CaSR-deficient mice Histamine alone was used. In a subsequent series of experiments Zinc was added. Results: In the presence of functional CaSR the inhibitory effect of Zinc on gastric acid secretion was significantly higher than that seen in CaSRdeficient mice, suggesting the primary pathway for zinc action is at the level of the CaSR. Conclusion: This study shows the predominant role of the CaSR in Zinc-mediated inhibition of gastric acid secretion. Additionally this study suggests the importance of dietary zinc to modulate acid production. Failure to have sufficient zinc in the diet would result in reduced serum levels of zinc. This reduction in zinc could lead to an enhanced CaSR function and subsequent gastric acid hypersecretion even in the absence of hormonal or neuronal stimulation.