Secretory state regulates Zn 2+ transport in gastric parietal cell of the rabbit

Secretory compartments of neurons, endocrine cells, and exocrine glands are acidic and contain high levels of labile Zn 2+ . Previously, we reported evidence that acidity is regulated, in part, by the content of Zn 2+ in the secretory [i.e., tubulovesicle (TV)] compartment of the acid-secreting gastric parietal cell. Here we report studies focusing on the mechanisms of Zn 2+ transport by the TV compartment in the mammalian (rabbit) gastric parietal cell. Uptake of Zn 2+ by isolated TV structures was monitored with a novel application of the fluorescent Zn 2+ reporter N-(6-methoxy-8-quinolyl)- para-toluenesulfonamide (TSQ). Uptake was suppressed by removal of external ATP or blockade of H + -K + -ATPase that mediates luminal acid secretion. Uptake was diminished with dissipation of the proton gradient across the TV membrane, suggesting Zn 2+ /H + antiport as the connection between Zn 2+ uptake and acidity in the TV lumen. In isolated gastric glands loaded with the reporter fluozin-3, inhibition of H + -K + -ATPase arrested the flow of Zn 2+ from the cytoplasm to the TV compartment and secretory stimulation with forskolin enhanced vectorial movement of cytoplasmic Zn 2+ into the tubulovesicle/lumen (TV/L) compartment. Our findings suggest that Zn 2+ accumulation in the TV/L compartment is physiologically coupled to secretion of acid. These findings offer novel insight into mechanisms regulating Zn 2+ homeostasis in the gastric parietal cell and potentially other cells in which acidic subcellular compartments serve signature functional roles.