Secretory state regulates Zn2+ 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 Zn2+. Previously, we reported evidence that acidity is regulated, in part, by the content of Zn2+ in the secretory [i.e., tubulovesicle (TV)] compartment of the acid-secreting gastric parietal cell. Here we report studies focusing on the mechanisms of Zn2+ transport by the TV compartment in the mammalian (rabbit) gastric parietal cell. Uptake of Zn2+ by isolated TV structures was monitored with a novel application of the fluorescent Zn2+ 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 Zn2+/H+ antiport as the connection between Zn2+ 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 Zn2+ into the tubulovesicle/lumen (TV/L) compartment. Our findings suggest that Zn2+ accumulation in the TV/L compartment is physiologically coupled to secretion of acid. These findings offer novel insight into mechanisms regulating Zn2+ homeostasis in the gastric parietal cell and potentially other cells in which acidic subcellular compartments serve signature functional roles.
Naik
Haley B
HB
Department of Surgery, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Beshire
Melissa
M
Walsh
Breda M
BM
Liu
Jingjing
J
Soybel
David I
DI
D000634:Aminoquinolines; D000818:Animals; D002413:Cations, Divalent / Q000378:metabolism; D005456:Fluorescent Dyes; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D017136:Ion Transport; D010295:Parietal Cells, Gastric / Q000378:metabolism*; D011817:Rabbits; D014105:Tosyl Compounds
D000634:Aminoquinolines; D002413:Cations, Divalent; D005456:Fluorescent Dyes; D014105:Tosyl Compounds; C061730:N-(6-methoxy-8-quinolyl)-4-toluenesulfonamide; D017506:H(+)-K(+)-Exchanging ATPase
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